How Common Is Signal-Intensity Increase in Optic Nerve Segments on 3D Double Inversion Recovery Sequences in Visually Asymptomatic Patients with Multiple Sclerosis?

BACKGROUND AND PURPOSE:In postmortem studies, subclinical optic nerve demyelination is very common in patients with MS but radiologic demonstration is difficult and mainly based on STIR T2WI. Our aim was to evaluate 3D double inversion recovery MR imaging for the detection of subclinical demyelinating lesions within optic nerve segments.MATERIALS AND METHODS:The signal intensities in 4 different optic nerve segments (ie, retrobulbar, canalicular, prechiasmatic, and chiasm) were evaluated on 3D double inversion recovery MR imaging in 95 patients with MS without visual symptoms within the past 3 years and in 50 patients without optic nerve pathology. We compared the signal intensities with those of the adjacent lateral rectus muscle. The evaluation was performed by a student group and an expert neuroradiologist. Statistical evaluation (the Cohen κ test) was performed.RESULTS:On the 3D double inversion recovery sequence, optic nerve segments in the comparison group were all hypointense, and an isointense nerve sheath surrounded the retrobulbar nerve segment. At least 1 optic nerve segment was isointense or hyperintense in 68 patients (72%) in the group with MS on the basis of the results of the expert neuroradiologist. Student raters were able to correctly identify optic nerve hypersignal in 97%.CONCLUSIONS:A hypersignal in at least 1 optic nerve segment on the 3D double inversion recovery sequence compared with hyposignal in optic nerve segments in the comparison group was very common in visually asymptomatic patients with MS. The signal-intensity rating of optic nerve segments could also be performed by inexperienced student readers.

MR imaging contributes to not only the diagnosis and differential diagnosis of MS but also the monitoring and follow-up of patients.¹ T1-weighted postcontrast, T2-weighted, proton-density, FLAIR, and double inversion recovery (DIR) images are recommended to detect acute and chronic demyelinating lesions in typical locations.^1–9Acute optic neuritis is an inflammatory demyelination of the optic nerve causing acute visual loss.^10–13 After recovery, patients are often visually asymptomatic, but careful visual testing by visually evoked potentials, optical coherence tomography, and visual disability evaluation may reveal persistent slight visual deficits.^14–17 These deficits are also observed in patients without any history of previous acute optic neuritis due to a suspected subclinical disease known as subclinical optic nerve demyelination.^14–17Acute optic neuritis is easily diagnosed on MR imaging by focal nerve swelling and segmental T2-weighted hyperintensity, especially on STIR images or on fat-suppressed T2-weighted images and by segmental gadolinium enhancement on T1-weighted fat-suppressed images.^10,18–22 The enhancement is present for a mean of 30 days after the onset of visual symptoms.^21,23–31Subclinical optic nerve demyelination, however, is not easily visible on MR imaging. Routine T2-weighted images without fat suppression and contrast-enhanced T1-weighted FSE images do not show any signal abnormality in the affected optic nerve. Fat-suppressed T2-weighted FSE images, especially STIR T2-weighted images, may detect a signal-intensity abnormality in subclinical optic nerve demyelination.^23,32,33 The highly diagnostic value of fat-suppressed FLAIR images and fat-suppressed 3D DIR images in the detection of any pathologic signal intensity in the optic nerve has been evaluated in acute optic nerve demyelination.^10,34,35 In a few patients with subclinical optic nerve demyelination, signal-intensity abnormalities have been reported on 3D FLAIR.³⁴ However, there are few data about the use of the 3D DIR sequence in the evaluation of subclinical optic nerve demyelination.³⁶In our department, patients with MS are routinely and regularly monitored for disease progression by a standard protocol with 3D FLAIR, 3D DIR, T2-weighted FSE, and 3D T1-weighted postcontrast images. 3D DIR is added to our standard protocol for improved detection of juxtacortical, cortical, and infratentorial demyelinating lesions.^1–9 On the basis of postmortem and clinical studies having already shown a high percentage of subclinical optic nerve demyelination with ongoing axonal loss in patients with MS,^37–41 we wanted to test 2 hypotheses: first, that it is possible to detect signal-intensity changes in optic nerve segments on the 3D DIR sequence without the additional application of a STIR T2-weighted sequence over the orbits in patients with MS without a history of clinically obvious visual loss and without a history of acute optic neuritis during the previous 3 years; and second, that the signal-intensity changes on 3D DIR are so obvious that even inexperienced readers can detect them. This second hypothesis is important because in our department, MR imaging examinations of patients with MS are evaluated not only by trained neuroradiologists but also general radiologists. Therefore, it is desirable that the lack of neuroradiologic experience be compensated by the application of an easily readable MR image, and the 3D DIR sequence is routinely acquired in our department for the follow-up of patients with MS.For comparison, the signal intensities of normal healthy optic nerve segments in patients evaluated by the identical 3D DIR sequence for different diseases (ie, epileptic seizures and posttraumatic sequelae) were analyzed as well.     

T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease

BACKGROUND AND PURPOSE:Signal intensity increases possibly suggestive of gadolinium retention have recently been reported on unenhanced T1-weighted images of the pediatric brain following multiple exposures to gadolinium-based MR contrast agents. Our aim was to determine whether T1 signal changes suggestive of gadolinium deposition occur in the brains of pediatric nonneurologic patients after multiple exposures to gadobenate dimeglumine.MATERIALS AND METHODS:Thirty-four nonneurologic patients (group 1; 17 males/17 females; mean age, 7.18 years) who received between 5 and 15 injections (mean, 7.8 injections) of 0.05 mmol/kg of gadobenate during a mean of 2.24 years were compared with 24 control patients (group 2; 16 males/8 females; mean age, 8.78 years) who had never received gadolinium-based contrast agents. Exposure to gadobenate was for diagnosis and therapy monitoring. Five blinded readers independently determined the signal intensity at ROIs in the dentate nucleus, globus pallidus, pons, and thalamus on unenhanced T1-weighted spin-echo images from both groups. Unpaired t tests were used to compare signal-intensity values and dentate nucleus–pons and globus pallidus–thalamus signal-intensity ratios between groups 1 and 2.RESULTS:Mean signal-intensity values in the dentate nucleus, globus pallidus, pons, and thalamus of gadobenate-exposed patients ranged from 366.4 to 389.2, 360.5 to 392.9, 370.5 to 374.9, and 356.9 to 371.0, respectively. Corresponding values in gadolinium-based contrast agent–naïve subjects were not significantly different (P > .05). Similarly, no significant differences were noted by any reader for comparisons of the dentate nucleus–pons signal-intensity ratios. One reader noted a difference in the mean globus pallidus–thalamus signal-intensity ratios (1.06 ± 0.006 versus 1.02 ± 0.009, P = .002), but this reflected nonsignificantly higher T1 signal in the thalamus of control subjects. The number of exposures and the interval between the first and last exposures did not influence signal-intensity values.CONCLUSIONS:Signal-intensity increases potentially indicative of gadolinium deposition are not seen in pediatric nonneurologic patients after multiple exposures to low-dose gadobenate.

Recent reports have detailed high signal intensity (SI) in certain brain areas (primarily the dentate nucleus [DN] and globus pallidus [GP]) on unenhanced T1-weighted images following multiple exposures to gadolinium-based contrast agents (GBCAs).^1–20 Many of these reports have focused on apparent differences between macrocyclic and open-chain “linear” GBCAs,^4–13 invariably associating progressive T1 hyperintensity with multiple exposures to linear GBCAs and concluding that observed T1 signal reflects the lower stability of these agents and thus a greater propensity for gadolinium (Gd) release and, subsequently, deposition in the brain. Among the more recent reports are several that describe retrospective assessments in pediatric patients.^15–19 Although each patient evaluated received just 1 specific linear GBCA (gadopentetate dimeglumine; Magnevist; Bayer HealthCare, Wayne, New Jersey), the study-based recommendations in each case were to consider carefully the use of all linear agents in pediatric subjects.Gadobenate dimeglumine (MultiHance; Bracco Diagnostics, Monroe, New Jersey) is an ionic open-chain, linear GBCA that differs fundamentally from gadopentetate and other extracellular GBCAs in having an aromatic substituent on the chelating molecule.²¹ Unique properties conferred by this substituent include increased R1-relaxivity,²² which permits the acquisition of diagnostically valid images with a reduced dose,²³ and liver-specificity, which permits gadobenate use for hepatobiliary-phase liver applications.²⁴ An additional benefit is increased molecular stability compared with gadopentetate, other linear agents, and certain macrocyclic agents.²⁵ Studies that have evaluated brain T1 signal intensities after multiple exposures to gadobenate have yielded conflicting results with one report demonstrating T1 signal increases, albeit to a lesser extent than with gadopentetate,¹⁰ and others demonstrating no direct changes.^11,12We aimed to determine whether multiple exposures to low-dose gadobenate for nonneurologic pathology results in T1 signal changes in the DN and GP of pediatric patients relative to that in age- and weight-matched GBCA-naïve control subjects.     

Quiet T1-Weighted Pointwise Encoding Time Reduction with Radial Acquisition for Assessing Myelination in the Pediatric Brain

BACKGROUND AND PURPOSE:T1-weighted pointwise encoding time reduction with radial acquisition (PETRA) sequences require limited gradient activity and allow quiet scanning. We aimed to assess the usefulness of PETRA in pediatric brain imaging.MATERIALS AND METHODS:We included consecutive pediatric patients who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios between WM and GM were compared in the cerebellar WM, internal capsule, and corpus callosum. The degree of myelination was rated by using 4-point scales at each of these locations plus the subcortical WM in the anterior frontal, anterior temporal, and posterior occipital lobes. Two radiologists made all assessments, and the intra- and interrater agreement was calculated by using intraclass correlation coefficients. Acoustic noise on MPRAGE and PETRA was measured.RESULTS:We included 56 patients 5 days to 14 years of age (mean age, 36.6 months) who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios for PETRA were significantly higher than those for MPRAGE (P < .05), excluding the signal ratio for cerebellar WM. Excellent intra- and interrater agreement were obtained for myelination at all locations except the cerebellar WM. The acoustic noise on PETRA (58.2 dB[A]) was much lower than that on MPRAGE (87.4 dB[A]).CONCLUSIONS:PETRA generally showed better objective imaging quality without a difference in subjective image-quality evaluation and produced much less acoustic noise compared with MPRAGE. We conclude that PETRA can substitute for MPRAGE in pediatric brain imaging.

MR imaging is widely used for brain assessment in both adults and children, enabling the noninvasive and detailed evaluation of morphologic and functional abnormalities.^1,2 However, MR imaging has some drawbacks. Of note, an average scanning time of 20–30 minutes is usually required for a routine brain examination, during which the patient is subjected to loud acoustic noise. Consequently, the application of MR imaging is limited in infants and small children, who often need sedation to undergo MR imaging.^3–5 Even under sedation, the acoustic noise from MR imaging can make children restless or cause them to awaken, resulting in severe motion artifacts or incomplete examinations.With the increased use of MR imaging in children, it is important to reduce the loudness of MR imaging scanners to ensure that scans are completed with minimal distress to the child and minimal artifacts on the acquired images. Because the acoustic noise of MR imaging is produced by the vibration of gradient coils during the scan, noise reduction can be achieved by decreasing the noise from these coils. One such method involves sealing gradient coils in a vacuum chamber.⁶ More recently, several methods have been introduced to reduce acoustic noise that do not involve altering the scanner hardware. These techniques include the use of acoustically optimized pulse shapes of the gradient coils to cancel single frequencies extended by a second frequency,⁷ ultrashort TE sequences such as zero TE,⁸ sweep imaging with Fourier transformation,⁹ and pointwise encoding time reduction with radial acquisition (PETRA).¹⁰ Of these, PETRA requires limited gradient activity, which creates a particularly quiet MR imaging scan.¹⁰ Considering that quiet sequences should be useful for reducing patient stress during the scan, this technique might particularly benefit children. PETRA sequencing uses an inversion recovery pulse to yield T1WI, which is a basic MR imaging sequence that can be used to assess myelination in children.In this study, we therefore aimed to compare the measurements of pediatric brain myelination obtained by using a quiet T1-weighted PETRA sequence with those captured by MPRAGE to assess the suitability of PETRA for pediatric brain imaging.     

Comparison of Sagittal FSE T2, STIR,and T1-Weighted Phase-Sensitive Inversion Recovery in the Detection of Spinal Cord Lesions in MS at 3T

BACKGROUND AND PURPOSE:Determining the diagnostic accuracy of different MR sequences is essential to design MR imaging protocols. The purpose of the study was to compare 3T sagittal FSE T2, STIR, and T1-weighted phase-sensitive inversion recovery in the detection of spinal cord lesions in patients with suspected or definite MS.MATERIALS AND METHODS:We performed a retrospective analysis of 38 patients with suspected or definite MS. Involvement of the cervical and thoracic cord segments was recorded on sagittal FSE T2, STIR, and T1-weighted phase-sensitive inversion recovery sequences independently by 2 readers. A consensus criterion standard read was performed with all sequences available. Sensitivity, specificity, and interobserver agreement were calculated for each sequence.RESULTS:In the cervical cord, the sensitivity of T1-weighted phase-sensitive inversion recovery (96.2%) and STIR (89.6%) was significantly higher (P < .05) than that of FSE T2 (50.9%), but no significant difference was found between T1-weighted phase-sensitive inversion recovery and STIR. In the thoracic cord, sensitivity values were 93.8% for STIR, 71.9% for FSE T2, and 50.8% for T1-weighted phase-sensitive inversion recovery. Significant differences were found for all comparisons (P < .05). No differences were detected in specificity. Poor image quality and lower sensitivity of thoracic T1-weighted phase-sensitive inversion recovery compared with the other 2 sequences were associated with a thicker back fat pad.CONCLUSIONS:The use of an additional sagittal sequence other than FSE T2 significantly increases the detection of cervical and thoracic spinal cord lesions in patients with MS at 3T. In the cervical segment, both STIR and T1-weighted phase-sensitive inversion recovery offer high sensitivity and specificity, whereas in the thoracic spine, STIR performs better than T1-weighted phase-sensitive inversion recovery, particularly in patients with a thick dorsal fat pad.

MR imaging of the spinal cord is an important diagnostic technique in MS because the prevalence of spinal cord abnormalities in patients with clinically isolated syndrome is as high as 42%.¹ In clinically diagnosed MS, spinal cord involvement reaches 75%–92%, depending on the series.^2–4 The presence of asymptomatic cord lesions contributes to the demonstration of dissemination in space in the McDonald 2010 criteria for MS, and imaging of the spinal cord allows an increase of 18.3% in the number of patients meeting the diagnostic criteria.⁵ The presence of spinal cord lesions not only facilitates diagnosing MS but is also predictive of conversion to clinically definite MS, especially in patients with nonspinal clinically isolated syndrome who do not fulfill brain MR imaging criteria.⁶ Moreover, spinal cord lesions in MS can occur in isolation in 5% of patients, particularly in primary-progressive MS.⁷Spinal cord imaging is challenging because the spinal cord is a small and mobile structure.⁸ In addition, its anatomic location makes it prone to ghosting artifacts caused by the heart and great vessels as well as truncation artifacts. 3T MR imaging compared with 1.5T is more prone to artifacts caused by B₁ field inhomogeneity,⁹ susceptibility, vascular pulsation, and chemical shift.^10,11 In addition, 3T MR imaging has a higher energy deposit within the tissue, resulting in a higher specific absorption rate than lower field scanners. These problems can be partially solved with various technical adjustments and fast (parallel) imaging.¹²Traditionally, the spinal cord in patients with MS has been imaged by using sagittal and axial FSE T2/proton density sequences. Additional sequences, including STIR^13,14 and T1 inversion recovery,¹⁵ have shown promise by increasing lesion visibility, particularly at 3T, in which conventional FSE T2 and proton density images are frequently unsatisfactory.¹⁶ STIR has proved very useful as a complementary sequence in the detection of MS lesions but cannot be used in isolation due to its lower specificity.^13,14 Numerous studies have demonstrated the superiority of STIR over T2 at 1.5T,^{13,14,17–19} and 1 study¹⁵ also showed the advantages of STIR at 3T in the cervical cord. To our knowledge, no studies have been performed in the thoracic cord comparing sagittal FSE T2 and STIR. A recent publication showed the advantages of T1-weighted phase-sensitive inversion recovery (PSIR) for the detection of cervical spinal cord lesions in MS at 3T.¹⁶ PSIR has been shown to improve lesion localization and boundary definition over STIR in the cervical spinal cord, but it has not been tested in the thoracic cord.¹⁶The aim of our study was to compare the sensitivity and specificity of sagittal STIR, PSIR, and FSE T2 in the detection of MS spinal cord lesions at 3T, in both the cervical and thoracic segments.     

Optimal MR Plaque Imaging for Cervical Carotid Artery Stenosis in Predicting the Development of Microembolic Signals during Exposure of Carotid Arteries in Endarterectomy: Comparison of 4 T1-Weighted Imaging Techniques

BACKGROUND AND PURPOSE:Preoperative identification of plaque vulnerability may allow improved risk stratification for patients considered for carotid endarterectomy. The present study aimed to determine which plaque imaging technique, cardiac-gated black-blood fast spin-echo, magnetization-prepared rapid acquisition of gradient echo, source image of 3D time-of-flight MR angiography, or noncardiac-gated spin-echo, most accurately predicts development of microembolic signals during exposure of carotid arteries in carotid endarterectomy.MATERIALS AND METHODS:Eighty patients with ICA stenosis (≥70%) underwent the 4 sequences of preoperative MR plaque imaging of the affected carotid bifurcation and then carotid endarterectomy under transcranial Doppler monitoring of microembolic signals in the ipsilateral middle cerebral artery. The contrast ratio of the carotid plaque was calculated by dividing plaque signal intensity by sternocleidomastoid muscle signal intensity.RESULTS:Microembolic signals during exposure of carotid arteries were detected in 23 patients (29%), 3 of whom developed new neurologic deficits postoperatively. Those deficits remained at 24 hours after surgery in only 1 patient. The area under the receiver operating characteristic curve to discriminate between the presence and absence of microembolic signals during exposure of the carotid arteries was significantly greater with nongated spin-echo than with black-blood fast spin-echo (difference between areas, 0.258; P < .0001), MPRAGE (difference between areas, 0.106; P = .0023), or source image of 3D time-of-flight MR angiography (difference between areas, 0.128; P = .0010). Negative binomial regression showed that in the 23 patients with microembolic signals, the contrast ratio was associated with the number of microembolic signals only in nongated spin-echo (risk ratio, 1.36; 95% confidence interval, 1.01–1.97; P < .001).CONCLUSIONS:Nongated spin-echo may predict the development of microembolic signals during exposure of the carotid arteries in carotid endarterectomy more accurately than other MR plaque imaging techniques.

For appropriately selected patients, carotid endarterectomy (CEA) can effectively prevent stroke,^1–3 with few neurologic deficits observed immediately following the procedure. Surgical site embolism represents >70% of intraoperative procedure-related strokes.⁴ When one monitors the middle cerebral artery by using intraoperative transcranial Doppler (TCD), microembolic signals (MES) are detected in >90% of patients undergoing CEA^4–6; however, the quality and quantity of MES detected depends on the stage of CEA.^5–7 During exposure procedures for the carotid arteries, plaque that represents a source of emboli and has not been removed remains exposed to blood flow. Under such conditions, manipulation of the carotid arteries can dislodge emboli from the surgical site into the intracranial arteries.⁸ Furthermore, because the target vessel remains closed during the exposure procedure, detectable MES are thought to represent solid masses, such as thrombi, necrosis, or lipid.⁶ In contrast, once the walls of the carotid arteries are cut for endarterectomy, a high number of harmless gaseous MES may develop during carotid declamping due to air entering the lumen of the arteries.^6,9 Detection of MES during the exposure procedure has been shown to correlate with postoperative neurologic deficits immediately after CEA.^5–7,9–11Several investigators have compared MES during the exposure procedure for the carotid arteries in CEA with histopathologic findings of excised carotid plaque and have demonstrated that development of the MES was strongly associated with vulnerable carotid plaques consisting primarily of intraplaque hemorrhage and/or intraluminal thrombus.^12,13 Intraplaque hemorrhage might cause formation of intraluminal thrombus likely due to chemical mediators, increased stenosis, or changes in eddy currents, though the associations among these remain unclear. Other research has shown that more cerebrovascular adverse events related to CEA occurred in patients with atheromatous plaques compared with patients with fibrous plaques.⁹ Preoperative identification of plaque vulnerability may thus allow improved risk stratification for patients considered for CEA.Intraplaque characteristics are generally assessed by using MR imaging based on T1-weighted sequences,¹⁴ and the detection of intraplaque hemorrhage on preoperative MR imaging is associated with the development of MES during the procedure for exposure of the carotid arteries.¹² However, there has been inconsistency among published findings on vulnerable plaques.¹⁵ This could be due to interinstitutional differences in the methodology for such imaging techniques as cardiac-gated black-blood fast spin-echo (BB-FSE),^16–19 magnetization-prepared rapid acquisition of gradient echo,^12,20–22 source image of 3D time-of-flight MR angiography (SI-MRA),²³ and noncardiac-gated spin-echo (SE).^15,24,25 Although the cardiac-gated BB-FSE method is most commonly used for T1-weighted MR plaque imaging,^17,18 the TR is dependent on a single R-R interval from electrocardiography, which occasionally results in an overly long TR to diminish proton density–weighted contrast and to enhance T1-weighted contrast.²⁵In addition to cardiac gating, proton density–weighted contrast is preserved when using T1-weighted spoiled gradient-echo techniques, which are generally used for MRA.²³ The use of T1-weighted spoiled gradient-echo techniques on SI-MRA could result in insufficient contrast between fibrous and lipid/necrotic plaques.¹⁵ Originally developed for direct thrombus imaging, MPRAGE is a modified sequence in which the TI is set to permit black-blood effects.²¹ Because the signal intensity of the lipid/necrotic component tends to show T1 values similar to those of blood, the intensity can theoretically be attenuated.¹⁵ The substantial influence of the proton density and inversion recovery pulse can be avoided in nongated SE; however, this sequence requires a relatively long acquisition time and is known to be susceptible to patient motion even when motion correction is used.¹⁵ Among these 4 kinds of imaging techniques, substantial variation is observed in the contrast provided by T1-weighted MR plaque imaging and its ability to characterize intraplaque components. Furthermore, quantitative color-coded MR plaque imaging performed by using the nongated SE sequence has recently been shown to provide accurate evaluation of the composition (ie, fibrous tissue, lipid/necrosis, or hemorrhage) of excised carotid plaques compared with histopathologic findings in patients undergoing CEA.²⁶The purpose of the present study was thus to determine which plaque imaging technique, BB-FSE, MPRAGE, SI-MRA, or nongated SE, all of which are variations of T1-weighted imaging, can most accurately predict development of MES during exposure of the carotid arteries in CEA.     

Cumulative Dose of Macrocyclic Gadolinium-Based Contrast Agent Improves Detection of Enhancing Lesions in Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE:Gadolinium-enhanced MR imaging is currently the reference standard for detecting active inflammatory lesions in patients with multiple sclerosis. The sensitivity of MR imaging for this purpose may vary according to the physicochemical characteristics of the contrast agent used and the acquisition strategy. The purpose of this study was to compare detection of gadolinium-enhancing lesions or active disease following a single or cumulative dose of a macrocyclic gadolinium-based contrast agent with different image acquisition delays in patients with clinically isolated syndrome or relapsing multiple sclerosis.MATERIALS AND METHODS:All patients received a first dose (0.1 mmol/kg) of gadobutrol and, 20 minutes later, a second dose (0.1 mmol/kg), with a cumulative dose of 0.2 mmol/kg. Two contrast-enhanced T1-weighted sequences were performed at 5 and 15 minutes after the first contrast administration, and 2 additional T1-weighted sequences at 5 and 15 minutes after the second contrast administration with a 3T magnet.RESULTS:One hundred fifteen patients were considered evaluable. A significantly larger number of lesions were detected in scans obtained at 5 and 15 minutes after the second contrast injection compared with scans obtained at 5 and 15 minutes after the first injection (P < .001). The number of patients with active lesions on MR imaging was significantly higher after the second dose administration (52.0%, first dose versus 59.2%, second dose; P < .001).CONCLUSIONS:Cumulative dosing of a macrocyclic gadolinium-based contrast agent increases detection of enhancing lesions and patients with active lesions. These data could be considered in the design of MR imaging protocols aimed at detecting active multiple sclerosis lesions.

Gadolinium-enhanced MR imaging is currently the reference standard for detecting inflammatory demyelinating lesions associated with increased permeability of the blood-brain barrier in patients with multiple sclerosis, and is commonly used as a marker of acute focal inflammatory activity.^1,2 The sensitivity of the technique for this purpose may vary according to the physicochemical characteristics of the contrast agent used and the acquisition strategy (eg, delay between injection and image acquisition, contrast dose, field strength, and parameters of the postinjection T1-weighted sequence).^3–12 A large body of evidence has indicated that various approaches can increase the visibility of contrast-enhancing lesions and lead to a notable improvement in sensitivity.^{3,4,8,9,12–15} One potential strategy that has not yet been explored is the combination of an increased contrast dose and a longer delay time at 3T MR imaging with a 2D gradient recalled-echo (GRE) T1-weighted sequence. To examine this option, we designed the present open-label, prospective study to assess the advantages of combining a high-field-strength MR imaging magnet (3T) and a cumulative gadolinium dose (0.1 mmol/kg + 0.1 mmol/kg) at different delay times compared with a single dose (0.1 mmol/kg) to detect active lesions in patients with clinically isolated syndrome (CIS) or relapsing MS. The hypothesis was that the combined advantages of a cumulative gadolinium dose and a longer delay time would significantly increase the detection rate of active lesions and the percentage of patients showing disease activity, measures that have a strong impact for the diagnosis of the disease, therapy optimization, and predicting disease course and treatment response.^1,2,16     

Radiomic Phenotypes Distinguish Atypical Teratoid/Rhabdoid Tumors from Medulloblastoma

BACKGROUND AND PURPOSE:Atypical teratoid/rhabdoid tumors and medulloblastomas have similar imaging and histologic features but distinctly different outcomes. We hypothesized that they could be distinguished by MR imaging–based radiomic phenotypes.MATERIALS AND METHODS:We retrospectively assembled T2-weighted and gadolinium-enhanced T1-weighted images of 48 posterior fossa atypical teratoid/rhabdoid tumors and 96 match-paired medulloblastomas from 7 institutions. Using a holdout test set, we measured the performance of 6 candidate classifier models using 6 imaging features derived by sparse regression of 900 T2WI and 900 T1WI Imaging Biomarker Standardization Initiative–based radiomics features.RESULTS:From the originally extracted 1800 total Imaging Biomarker Standardization Initiative–based features, sparse regression consistently reduced the feature set to 1 from T1WI and 5 from T2WI. Among classifier models, logistic regression performed with the highest AUC of 0.86, with sensitivity, specificity, accuracy, and F1 scores of 0.80, 0.82, 0.81, and 0.85, respectively. The top 3 important Imaging Biomarker Standardization Initiative features, by decreasing order of relative contribution, included voxel intensity at the 90th percentile, inverse difference moment normalized, and kurtosis—all from T2WI.CONCLUSIONS:Six quantitative signatures of image intensity, texture, and morphology distinguish atypical teratoid/rhabdoid tumors from medulloblastomas with high prediction performance across different machine learning strategies. Use of this technique for preoperative diagnosis of atypical teratoid/rhabdoid tumors could significantly inform therapeutic strategies and patient care discussions.

Atypical teratoid/rhabdoid tumors (ATRTs) are rare-but-aggressive neoplasms that often affect very young children.^1,2 They are classically characterized by rhabdoid cells and divergent differentiation along neuroectodermal, mesenchymal, and epithelial lines. However, many ATRTs often lack rhabdoid cells and are simply dense, small, round, blue cell–rich lesions that mimic medulloblastomas (MBs, Online Supplemental Data).^3,4 Whereas most ATRTs may be distinguished from MBs by immunohistochemical confirmation of SMARCB1 (INI1/BAF47/hSNF5) loss (Online Supplemental Data),^4-7 up to 22% of ATRTs retain the protein marker.^5,8,9Presurgical distinction of ATRT from MB is not possible by human interpretation of MR imaging; both primarily occupy the posterior fossa, share low T1- and T2-weighted intensities and variable enhancement, and have a reduced diffusion characteristic of densely packed cellular tumors (Online Supplemental Data).^10-13 However, if it were possible, this distinction could add value because their different behaviors demand different treatment strategies. Median survival for patients with ATRTs is approximately 1 year, while the 5-year survival rate for pediatric MB is approximately 70%.^14-18 Thus, an anticipated diagnosis of ATRT may prompt discussion of maximal surgical resection and aggressive adjuvant therapy.^19,20Recent advances in machine learning and computer vision in medicine offer new potentials for precision in oncology, whether it is for tumor subgroup classification or prognosis. For example, feature extraction, such as in radiomics, enables mining of high-dimensional, quantitative image features that facilitate data-driven, predictive modeling. The resulting computational algorithm assigns probabilities for diagnoses and outcomes on the basis of its quantitative analysis of tumor voxels on imaging.^21-23 While studies have reported various machine learning approaches to MR imaging–based evaluation of pediatric brain tumors, no study has examined quantitative MR imaging features that distinguish ATRT from MB, in part, due to the rarity of ATRT.^{13,19, 24-27}Radiomics has the potential to not only uncover quantitative image features that may otherwise be imperceptible to the human eye but also offers interpretability of computational features that drive model prediction—a potential advantage over deep learning, in which learned features remain opaque. In this multicenter study, we applied machine learning to uncover MR imaging–based radiomic phenotypes that distinguish ATRT from MB.     

Transition into Driven Equilibrium of the Balanced Steady-State Free Precession as an Ultrafast Multisection T2-Weighted Imaging of the Brain

BACKGROUND AND PURPOSE:Current T2-weighted imaging takes >3 minutes to perform, for which the ultrafast transition into driven equilibrium (TIDE) technique may be potentially helpful. This study qualitatively and quantitatively evaluates the imaging of transition into driven equilibrium of the balanced steady-state free precession (TIDE) compared with TSE and turbo gradient spin-echo on T2-weighted MR images.MATERIALS AND METHODS:Thirty healthy volunteers were examined with T2-weighted images by using TIDE, TSE, and turbo gradient spin-echo sequences. Imaging was evaluated qualitatively by 2 independent observers on the basis of a 4-point rating scale regarding contrast characteristics and artifacts behavior. Image SNR and contrast-to-noise ratio were quantitatively assessed.RESULTS:TIDE provided T2-weighted contrast similar to that in TSE and turbo gradient spin-echo with only one-eighth of the scan time. TIDE showed gray-white matter differentiation and iron-load sensitivity inferior that of TSE and turbo gradient spin-echo, but with improved motion artifacts reduction on qualitative scores. Nonmotion ghosting artifacts were uniquely found in TIDE images. The overall SNRs of TSE were 1.9–2.0 times those of turbo gradient spin-echo and 1.7–2.2 times of those of TIDE for brain tissue (P < .0001). TIDE had a higher contrast-to-noise ratio than TSE (P = .169) and turbo gradient spin-echo (P < .0001) regarding non-iron-containing gray matter versus white matter. TIDE had a lower contrast-to-noise ratio than turbo gradient spin-echo and TSE (P < .0001) between iron-containing gray matter and white matter.CONCLUSIONS:TIDE provides T2-weighted images with reduced scan times and reduced motion artifacts compared with TSE and turbo gradient spin-echo with the trade-off of reduced SNR and poorer gray-white matter differentiation.

T2-weighted MR images are commonly used to depict gross pathologic changes of the brain, including tumor, infarction, ischemia, white matter demyelination, inflammation, edema, and so forth.^1–4 The turbo spin-echo sequence is a method currently used for routine T2WI examination in the brain and in other extracranial regions.^5,6 In daily practice, it often takes >3 minutes to obtain 1 set of 2D TSE T2WIs on a certain plane.^5–7 Accordingly, it might take as long as 10 minutes to obtain T2WI on 3 orthogonal planes by using TSE. Although 3D imaging techniques have been developed to acquire T2WI, they still take as long as 6–8 minutes of acquisition time,^8–10 which makes them prone to motion artifacts and hampers their clinical application in daily practice.There is an increasing need for a fast imaging technique to acquire T2WI of the brain in patients with motion during MR imaging. In 2000, Chung et al¹¹ demonstrated the advantage of a fast imaging with steady-state free precession to freeze the fetal motion during MR imaging. However, true fast imaging with steady-state precession carries a contrast known as T2/T1 rather than T2-weighted. The transition into driven equilibrium is a variant of the balanced steady-state free precession technique, inheriting characteristics of balanced steady-state free precession like high SNR efficiency and flow compensation. Different from the T2/T1 contrast of conventional balanced steady-state free precession,^11,12 pure T2 contrast or T2-weighted contrast with fat suppression can be rendered by transition into driven equilibrium (TIDE) theoretically, depending on the sampling strategy of the contrast-determining central k-space.^13–17 The typical scan time of TIDE for a single section is approximately 1 second, which is desirable, especially when 3-plane multisection T2WIs are considered for clinical practice, such as for rapid screening or diagnosis. Before applying them to daily practice, however, the imaging quality and characteristics of TIDE need to be evaluated.We assume that TIDE could also provide T2-weighted imaging contrast similar to that in other pulse sequences, including TSE and turbo gradient spin-echo (TGSE). In this study, we aimed to qualitatively and quantitatively evaluate TIDE compared with TSE and TGSE in T2-weighted brain MR images.     

Detection of Calcifications in Retinoblastoma Using Gradient-Echo MR Imaging Sequences: Comparative Study between In Vivo MR Imaging and Ex Vivo High-Resolution CT

BACKGROUND AND PURPOSE:Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard.MATERIALS AND METHODS:Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1–71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated.RESULTS:All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI.CONCLUSIONS:Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.

Retinoblastoma is generally treated on the basis of funduscopic, sonography, and imaging findings without prior histopathologic confirmation of diagnosis. The prevalence of calcifications is approximately 85%¹ and is considered the key finding in differentiating retinoblastoma from simulating lesions (Coats disease, persistent hyperplastic primary vitreous, or toxocara endophthalmitis) in young children.² Very rare lesions such as medulloepithelioma and retinocytoma may also have calcifications and hence occasionally cause difficulty with clinical and radiologic differentiation.³Sonography is the most commonly used imaging technique for the evaluation of intraocular tumors. The combination of funduscopy and sonography allows the identification of calcifications in 91%–95% of all patients with newly diagnosed retinoblastoma.⁴ Sensitivity to small calcifications decreases, however, in the presence of massive retinal detachment, vitreous hemorrhage, and subretinal fluid, potentially hampering the confirmation of the diagnosis. In these complicated eyes, CT is generally the method of choice for studying intraocular calcifications, with reported sensitivities of 81%–96%.⁵ Its diagnostic performance in staging retinoblastoma disease extent is limited, however, and the theoretic increased risk of radiation-induced cataracts and fatal cancers in children who are exposed to ionizing radiation should be considered.⁶ Patients with hereditary retinoblastoma in particular are at an even higher risk of developing radiation-induced tumors compared with healthy children.MR imaging is the noninvasive technique of choice for the evaluation of retinoblastoma. The combination of sonography and MR imaging is considered first-line diagnostic imaging in the evaluation of children with suspected retinoblastoma, surpassing CT.⁷ However, MR imaging does not allow reliable identification of tumoral calcifications on routinely used clinical sequences. The lack of spatial resolution with standard clinical sequences provides an additional challenge for the visualization of small punctate tumoral calcifications. Scarce data on high-resolution ocular MR imaging by using surface coils do, however, suggest that calcifications can be detected with reasonable diagnostic accuracy.⁸Gradient-echo T2*-weighted imaging sequences are sensitive to susceptibility differences among tissues that cause magnetic field inhomogeneity leading to signal loss, and T2*WI is used to depict blood products, deoxygenated venous blood in dilated vessels (venous congestion), and calcifications.^9,10 Previous work by Galluzzi et al¹¹ showed that T2*WI can be a feasible technique for detecting intraocular calcifications because calcified areas in retinoblastoma emerged as hypointense foci of signal-intensity voids (SIVs) within the soft-tissue mass. Most of the SIVs on T2*WI correlated with spots of intratumoral calcifications on CT. Whether the shape and spatial arrangement of the intraocular SIVs on MR imaging could be matched with calcifications on CT was not investigated.The purpose of our study was to assess the performance of gradient-echo T2*WI in the visualization and morphologic evaluation of retinoblastoma calcifications and to compare T2*WI with ex vivo CT scans of the enucleated eyes as the criterion standard.     

Associations between Cerebral Embolism and Carotid Intraplaque Hemorrhage during Protected Carotid Artery Stenting

BACKGROUND AND PURPOSE:Carotid artery stent placement in patients with intraplaque hemorrhage remains controversial because of the incidence of cerebral embolism after the procedure. The purpose of this study is to determine if intraplaque hemorrhage is a significant risk factor for cerebral embolism during carotid artery stent placement.MATERIALS AND METHODS:This prospective study assessed 94 consecutive patients with severe carotid stenosis. These patients underwent preprocedural carotid MR imaging and postprocedural DWI after carotid artery stent placement. Intraplaque hemorrhage was defined as the presence of high signal intensity within the carotid plaque that was >200% of the signal from the adjacent muscle on MPRAGE. We then analyzed the incidence of postprocedural ipsilateral ischemic events on DWI and primary outcomes within 30 days of carotid artery stent placement.RESULTS:Forty-three patients (45.7%) had intraplaque hemorrhage on an MPRAGE image. There was no significant difference in the incidence of postprocedural ipsilateral ischemic events and primary outcomes between the intraplaque hemorrhage and non–intraplaque hemorrhage group. However, postprocedural ipsilateral ischemic events were more frequently observed in the symptomatic group (17/41 [41.5%]) than in the asymptomatic group (8/53 [15.1%]; P = .005).CONCLUSIONS:Intraplaque hemorrhage was not a significant risk factor for cerebral embolism during carotid artery stent placement in patients with severe carotid stenosis. Symptomatic patients should receive more careful treatment during carotid artery stent placement because of the higher risk of postprocedural ipsilateral ischemic events.

Extracranial carotid artery stenosis is considered a causative factor in 20%–30% of all strokes.^1–3 Large randomized clinical trials showed that carotid endarterectomy is superior to carotid artery stent placement (CAS) for the management of carotid artery stenosis.^4–6 Other randomized clinical trials showed that CAS and carotid endarterectomy offer similar efficacy.⁷ Although indications for CAS remain controversial, CAS has emerged as a less-invasive treatment that requires shorter hospital times than carotid endarterectomy.Some studies found a relationship between the baseline presence of carotid intraplaque hemorrhage (IPH) and the development of ischemic stroke in previously asymptomatic and symptomatic patients.^8–10 IPH is associated with plaque progression and, consequently, induces luminal narrowing. Thus, IPH may serve as a measure of risk for the development of future ischemic stroke. The risk of cerebral embolism after CAS in patients with IPH is controversial. Yoshimura et al¹¹ reported that a high-intensity signal on TOF MRA indicates that carotid plaques are at high risk for cerebral embolism during stent placement. However, Yoon et al¹² reported that protected CAS seems to be safe in patients with severe carotid stenosis and IPH. This study did not perform DWI to evaluate ipsilateral ischemic lesions. In addition, these studies used TOF imaging to detect IPH. Alternative techniques proposed for more accurate detection of IPH include heavily T1-weighted techniques, such as the MPRAGE sequence. Ota et al¹³ reported that the MPRAGE sequence demonstrated higher diagnostic capability in detecting IPH when compared with conventional T1-weighted sequences or TOF sequences.We prospectively designed the study with the following inclusion criteria: 1) preoperative multicontrast carotid plaque MR; 2) protected CAS; 3) postprocedural imaging, including DWI and noncontrast CT within 24 hours; and 4) clinical outcomes after 30 days. The aim of this study was to determine whether IPH is a significant risk factor for cerebral embolism during CAS.     

Comparing 3T T1-Weighted Sequences in Identifying Hyperintense Punctate Lesions in Preterm Neonates

BACKGROUND AND PURPOSE:The loss of contrast on T1-weighted MR images at 3T may affect the detection of hyperintense punctate lesions indicative of periventricular leukomalacia in preterm neonates. The aim of the present study was to determine which 3T T1-weighted sequence identified the highest number of hyperintense punctate lesions and to explore the relationship between the number of hyperintense punctate lesions and clinical outcome.MATERIALS AND METHODS:The presence of hyperintense punctate lesions was retrospectively evaluated in 200 consecutive preterm neonates on 4 axial T1-weighted sequences: 3-mm inversion recovery and spin-echo and 1- and 3-mm reformatted 3D-fast-field echo. Statistically significant differences in the number of hyperintense punctate lesions were evaluated by using a linear mixed-model analysis. Logistic regression analysis was used to assess the relation between the number of hyperintense punctate lesions and neuromotor outcome at 3 months.RESULTS:Thirty-one neonates had at least 1 hyperintense punctate lesion indicative of periventricular leukomalacia in at least 1 of the 4 sequences. The 1-mm axial reformatted 3D-fast-field echo sequence identified the greatest number of hyperintense punctate lesions (P < .001). No statistically significant differences were found among the 3-mm T1-weighted sequences. The greater number of hyperintense punctate lesions detected by the 1-mm reformatted T1 3D-fast-field echo sequence in the central region of the brain was associated with a worse clinical outcome.CONCLUSIONS:At 3T, the 1-mm axial reformatted T1 3D-fast-field echo sequence identified the greatest number of hyperintense punctate lesions in the central region of preterm neonate brains, and this number was associated with neuromotor outcome.

Periventricular white matter injury is a major form of brain damage and the leading cause of chronic neurologic disability in survivors of preterm births.^1,2 Periventricular white matter injury includes a spectrum of cerebral damage that ranges from focal necrotic lesions (periventricular leukomalacia [PVL]) to diffuse myelination disturbances (diffuse periventricular white matter injury).^3–5 PVL is pathologically characterized by foci of coagulation necrosis in the periventricular white matter, which results in degeneration of cellular elements and, in particular, the premyelinating oligodendrocytes. The physiopathologic mechanism underlying PVL remains an important unresolved question.⁶Classic MR imaging signs of PVL are hyperintense punctate lesions (HPLs) on T1-weighted sequences, which infrequently may also appear hypointense on T2-weighted images.⁷ More severe presentations of PVL are either cavitation (cystic PVL) or glial scars and may be accompanied by a conspicuous reduction in white matter volume and ventricular enlargement.⁵ The causes determining the shortening of T1 and T2 signals in punctate PVL have not been completely established. Some authors hypothesized that signal shortening was determined by the presence of focal hemorrhages. Other studies hypothesized that the characteristic hyperintense signal on T1-weighted sequences was due to the contemporary presence of hemosiderin deposition, lipids from myelin breakdown, and dystrophic calcifications.⁷Preterm children with PVL present a high incidence of neurodevelopmental disabilities such as cerebral palsy; mental retardation; and psychologic, developmental, behavioral, and emotional disorders.⁸ Currently, an accurate method of identifying all preterm neonates (PNs) at risk of poor developmental outcome is not available, to our knowledge. Clinical risk factors, cranial sonography, and electroencephalography are used to study PNs around birth but are not optimal predictors of long-term outcome.^9,10 MR imaging can provide prognostic information concerning neuropsychological development. For example, PNs with a greater number of HPLs at MR imaging subsequently presented a worse motor and neurocognitive outcome. More specifically, the presence of HPLs in white matter regions traversed by the motor pathway was shown to be a useful predictor of motor outcome.^11,12 However, the use of MR imaging to screen PNs has been relatively limited because of the availability of the MR imaging systems, the complex management of neonates, and, above all, the low prognostic accuracy when no lesions are identified.^13,14To date, most MR imaging studies on PVL were performed by using MR imaging systems operating at 1.5T or lower field strengths. Liauw et al¹⁵ concluded that the spin-echo (SE) T1-weighted sequence scored best for detecting the presence of HPLs.Recently, the benefits from the improved signal-to-noise ratio and higher spatial resolution of MR imaging systems operating at 3T indicated the potential of this high magnetic field system for studying the neonatal brain, though the elongation of the T1 relaxation time at higher magnetic field strengths¹⁶ may bias the use of 3T scanners in preterm neonates due to the potential reduction of the sensitivity of T1 images for identifying HPLs.The aim of the present study was to determine which 3T T1-weighted sequence identified the highest number of HPLs in PNs studied at term-corrected age and to explore the relationship between the number/location of HPLs and the clinical outcome.     

Manual Segmentation of MS Cortical Lesions Using MRI: A Comparison of 3 MRI Reading Protocols

BACKGROUND AND PURPOSE:Double inversion recovery has been suggested as the MR imaging contrast of choice for segmenting cortical lesions in patients with multiple sclerosis. In this study, we sought to determine the utility of double inversion recovery for cortical lesion identification by comparing 3 MR imaging reading protocols that combine different MR imaging contrasts.MATERIALS AND METHODS:Twenty-five patients with relapsing-remitting MS and 3 with secondary-progressive MS were imaged with 3T MR imaging by using double inversion recovery, dual fast spin-echo proton-density/T2-weighted, 3D FLAIR, and 3D T1-weighted imaging sequences. Lesions affecting the cortex were manually segmented by using the following 3 MR imaging reading protocols: Protocol 1 (P1) used all available MR imaging contrasts; protocol 2 (P2) used all the available contrasts except for double inversion recovery; and protocol 3(P3) used only double inversion recovery.RESULTS:Six hundred forty-three cortical lesions were identified with P1 (mean = 22.96); 633, with P2 (mean = 22.6); and 280, with P3 (mean = 10). The counts obtained by using P1 and P2 were not significantly different (P = .93). The counts obtained by using P3 were significantly smaller than those obtained by using either P1 (P < .001) or P2 (P < .001). The intraclass correlation coefficients were P1 versus P2 = 0.989, P1 versus P3 = 0.615, and P2 versus P3 = 0.588.CONCLUSIONS:MR imaging cortical lesion segmentation can be performed by using 3D T1-weighted and 3D FLAIR images acquired with a 1-mm isotropic voxel size, supported by conventional T2-weighted and proton-density images with 3-mm-thick sections. Inclusion of double inversion recovery in this multimodal reading protocol did not significantly improve the cortical lesion identification rate. A multimodal approach is superior to using double inversion recovery alone.

Multiple sclerosis is an inflammatory and neurodegenerative disease that affects both the white matter and gray matter of the central nervous system. Postmortem immunohistochemical characterization of cortical lesions (CLs) has allowed the identification of a substantial burden of cortical GM lesions in patients with long-standing MS.^1–5 However, the prevalence of cortical lesions at earlier stages of MS is underexplored.⁶ As a result, an efficient, standardized MR imaging protocol for segmentation of CLs in early-stage MS has become an important research goal. Double inversion recovery (DIR) MR imaging has generally been selected because it enhances the conspicuity of GM by suppressing unwanted signal from both WM and CSF. However, DIR images have a low signal-to-noise ratio due to the application of 2 inversion pulses. They are also prone to hyperintense vascular artifacts, which can confound CL identification.^7–14In 2011, an international panel of experts formulated consensus recommendations for scoring CLs at 1.5T and 3T by using DIR.¹¹ As part of the recommendations, they noted that in the future, the additional use of other MR imaging contrasts (T1-weighted, T2-weighted, or fluid-attenuated inversion recovery images) in combination with DIR could improve the detection of cortical lesions by reducing the number of false-positives and false-negatives. Several groups have since reported on such multicontrast approaches for segmenting CLs. Examples include the following: 1) CL segmentation performed by using a single MR imaging contrast followed by subsequent verification of lesion labels on other contrasts¹³; 2) CL segmentation performed independently by using 2 different MR imaging contrasts, where a tight correlation between the counts is considered evidence that each MR imaging contrast yields counts proportional to the real lesion load¹⁵; 3) CL segmentation performed by using a single MR imaging contrast with the results subsequently reviewed by a second (more experienced) rater who uses other contrasts to resolve ambiguities/potential false-positives¹⁶; and 4) CL segmentation performed independently for each independent contrast, and then each count compared with the counts obtained from the other MR imaging contrasts to determine which one detects the highest number of lesions.¹⁷ The variability among these methods has led to difficulty in developing a standardized CL segmentation protocol.¹¹ Consequently, a major goal of this work was to identify a robust, multicontrast CL segmentation protocol that could be used with more generally available MR imaging pulse sequences at clinically accessible magnetic field strengths.According to the consensus recommendations, only type I leukocortical and type II intracortical lesions should be considered for radiologic scoring¹¹ in MS. However, type I lesions affecting both the cortex and the juxtacortical white matter are often difficult to differentiate from purely juxtacortical lesions. Consequently, these lesions can be misclassified. Type II lesions are the smallest and affect the cortex without reaching either the pial or white matter boundaries. These lesions are also challenging to detect visually by using 1.5T or 3T MR imaging. Subpial lesions (type III and IV), extending from the pial boundary down to the white matter surface, are not considered within the consensus guidelines for MR imaging at 1.5 and 3T due to their low detectability at these clinical field strengths. Even with these simplifying assumptions in place, CL identification has been highly variable.^10,13,18,19 The prevalence of MR imaging–identified intracortical lesions ranges from 8.2% to 46% across different published reports.^{10,12,13,18,19} This variability may partially reflect the variable sensitivity of current MR imaging protocols but also may indicate the inherent variability of cortical lesion involvement across MS disease stages and individual patients. Support for this hypothesis is provided by histology studies in which the percentage of intracortical lesions (type II) also shows a wide range: 7%–31% and 17%–71% when we consider types I and type II combined.^{1–6,19,20,21}A significant aim of our study was to simplify and improve the process of manual cortical lesion segmentation when using multiple MR imaging contrasts derived from 3T MR imaging. We specifically strived to identify a lesion-segmentation method with reduced variability and reduced false-positive identifications. To do this, we avoided classification of cortical lesions into subtypes.     

Imaging the Intracranial Atherosclerotic Vessel Wall Using 7T MRI: Initial Comparison with Histopathology

BACKGROUND AND PURPOSE:Several studies have attempted to characterize intracranial atherosclerotic plaques by using MR imaging sequences. However, dedicated validation of these sequences with histology has not yet been performed. The current study assessed the ability of ultra-high-resolution 7T MR imaging sequences with different image contrast weightings to image plaque components, by using histology as criterion standard.MATERIALS AND METHODS:Five specimens of the circle of Wills were imaged at 7T with 0.11 × 0.11 mm in-plane-resolution proton attenuation–, T1-, T2-, and T2*-weighted sequences (through-plane resolution, 0.11–1 mm). Tissue samples from 13 fiducial-marked locations (per specimen) on MR imaging underwent histologic processing and atherosclerotic plaque classification. Reconstructed MR images were matched with histologic sections at corresponding locations.RESULTS:Forty-four samples were available for subsequent evaluation of agreement or disagreement between plaque components and image contrast differences. Of samples, 52.3% (n = 23) showed no image contrast heterogeneity; this group comprised solely no lesions or early lesions. Of samples, 25.0% (n = 11, mostly advanced lesions) showed good correlation between the spatial organization of MR imaging heterogeneities and plaque components. Areas of foamy macrophages were generally seen as proton attenuation–, T2-, and T2*- hypointense areas, while areas of increased collagen content showed more ambiguous signal intensities. Five samples showed image-contrast heterogeneity without corresponding plaque components on histology; 5 other samples showed contrast heterogeneity based on intima-media artifacts.CONCLUSIONS:MR imaging at 7T has the image contrast capable of identifying both focal intracranial vessel wall thickening and distinguishing areas of different signal intensities spatially corresponding to plaque components within more advanced atherosclerotic plaques.

Intracranial atherosclerosis is emerging as one of the main causes of cerebral ischemic stroke and transient ischemic attack, with a high risk of recurrent ischemic events.¹ In recent years, several MR imaging sequences have been developed on 3T and 7T field strengths that specifically visualize the intracranial arterial vessel wall, enabling direct assessment of intracranial atherosclerotic plaques.^2–8 Similar to studies of carotid artery atherosclerosis almost a decade ago, several studies have recently attempted to characterize intracranial plaque components, such as intraplaque hemorrhage,^9,10 fibrous cap,¹¹ and lipid components, by using MR imaging.^12,13For the carotid arteries, much research has already been done validating image signal heterogeneity within the vessel wall with histology, the criterion standard.^14–20 Imaging carotid artery atherosclerosis has the advantage of easy access to ex vivo atherosclerotic plaque material for validation, using carotid endarterectomy specimens. It is now possible to image calcification, fibrous cap, intraplaque hemorrhage, and lipid-rich necrotic core in the carotid artery with moderate-to-good sensitivity and specificity by using multicontrast MR imaging.²⁰ Although 1 recent study showed promising preliminary results of plaque characterization by using a combined T1- and T2-weighted sequence²¹ compared with histology, dedicated validation with histology of intracranial vessel wall sequences with multiple image contrast weightings has not yet been performed. Therefore, whether MR imaging with multiple image contrast weightings has enough image contrast to also visualize various intracranial atherosclerotic plaque components remains a question.Validation of MR images with histology for intracranial atherosclerosis in vivo is much more cumbersome compared with carotid plaques, because no therapies (comparable with carotid endarterectomy) exist in which intracranial atherosclerotic plaques are removed. Furthermore, intracranial arteries are smaller than carotid (or other major peripheral) arteries,²² necessitating a high spatial resolution, and therefore high SNR, for plaque visualization. Because the SNR increases approximately linearly with field strength, 7T MR imaging might provide the spatial resolution necessary to image small atherosclerotic plaques.²² Furthermore, several dedicated intracranial vessel wall sequences at 7T have already shown promising results in the visualization of vessel wall lesions in vivo.In this feasibility study, ultra-high-resolution 7T MR imaging sequences with different image contrast weightings were developed and used in an ex vivo setting, to assess the ability (image contrast) of 7T MR imaging to image different intracranial atherosclerotic plaque components. For validation of our findings, results were compared with histology.     

A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

BACKGROUND AND PURPOSE:DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability.MATERIALS AND METHODS:Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects.RESULTS:T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation.CONCLUSIONS:Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

The era of quantitative MR imaging has arrived, allowing in vivo measurement of specific physical properties reflecting spinal cord (SC) microstructure and tissue damage.^1,2 Such measures have potential clinical applications, including improved diagnostic tools, objective monitoring for disease progression, and prediction of clinical outcomes.³ However, technical challenges such as artifacts, image distortion, and achieving acceptable SNR have led to limited reliability. Specialized pulse sequences and custom hardware have advanced the field but incur costs of increased complexity and acquisition time while creating barriers to portability and clinical adoption. Furthermore, quantitative MR imaging metrics often show wide ranges of normal values and confounding relationships with subject characteristics such as age,^4–8 for which most previous studies have not accounted.³Among the most promising SC quantitative MR imaging techniques are DTI and magnetization transfer (MT).^1–3 These provide measures of axonal integrity and myelin quantity that correlate with functional impairment in conditions such as degenerative cervical myelopathy (DCM)^5–7,9 and MS,^3,9 albeit with limited physiologic specificity (eg, fractional anisotropy [FA] reflects both demyelination and axonal injury).^10,11 SC cross-sectional area (CSA) computed from high-resolution anatomic images can measure atrophy (eg, in MS)¹² or the degree of SC compression in DCM.¹³ T2*-weighted imaging at 3T or higher field strengths offers high resolution and sharp contrast between SC WM and GM, allowing segmentation between these structures similar to that in phase-sensitive inversion recovery.^14,15 T2*WI also demonstrates hyperintensity in injured WM,^16–18 reflecting demyelination, gliosis, and increased calcium and nonheme iron concentrations.¹⁹ T2*WI signal intensity is not an absolute quantity, so we normalize its value in WM by the average GM signal intensity in each axial section, creating a novel measure of WM injury: T2*WI WM/GM ratio.²⁰We propose a multiparametric approach to cervical SC quantitative MR imaging with clinically feasible methods, including acceptable acquisition times, standard hardware/pulse sequences, and automated image analysis. Our protocol yields 4 measures of SC tissue injury (CSA, FA, MT ratio [MTR], and T2*WI WM/GM), for which this study establishes normative values in numerous ROIs. We characterize the variation of these metrics with age, sex, height, weight, cervical cord length, and rostrocaudal level and propose normalization methods. Finally, we assess test-retest reliability of FA, MTR, and T2*WI WM/GM and compare our DTI results against those with cardiac triggering.     

Measurement of Cortical Thickness and Volume of Subcortical Structures in Multiple Sclerosis: Agreement between 2D Spin-Echo and 3D MPRAGE T1-Weighted Images

BACKGROUND AND PURPOSE:Gray matter pathology is known to occur in multiple sclerosis and is related to disease outcomes. FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool (FIRST) have been developed for measuring cortical and subcortical gray matter in 3D-gradient-echo T1-weighted images. Unfortunately, most historical MS cohorts do not have 3D-gradient-echo, but 2D-spin-echo images instead. We aimed to evaluate whether cortical thickness and the volume of subcortical structures measured with FreeSurfer and FIRST could be reliably measured in 2D-spin-echo images and to investigate the strength and direction of clinicoradiologic correlations.MATERIALS AND METHODS:Thirty-eight patients with MS and 2D-spin-echo and 3D-gradient-echo T1-weighted images obtained at the same time were analyzed by using FreeSurfer and FIRST. The intraclass correlation coefficient between the estimates was obtained. Correlation coefficients were used to investigate clinicoradiologic associations.RESULTS:Subcortical volumes obtained with both FreeSurfer and FIRST showed good agreement between 2D-spin-echo and 3D-gradient-echo images, with 68.8%–76.2% of the structures having either a substantial or almost perfect agreement. Nevertheless, with FIRST with 2D-spin-echo, 18% of patients had mis-segmentation. Cortical thickness had the lowest intraclass correlation coefficient values, with only 1 structure (1.4%) having substantial agreement. Disease duration and the Expanded Disability Status Scale showed a moderate correlation with most of the subcortical structures measured with 3D-gradient-echo images, but some correlations lost significance with 2D-spin-echo images, especially with FIRST.CONCLUSIONS:Cortical thickness estimates with FreeSurfer on 2D-spin-echo images are inaccurate. Subcortical volume estimates obtained with FreeSurfer and FIRST on 2D-spin-echo images seem to be reliable, with acceptable clinicoradiologic correlations for FreeSurfer.

Gray matter pathology in patients with multiple sclerosis is present from the very early stages of the disease and has been related to long-term disability.^1,2 Therefore, in recent years, research has focused on obtaining accurate markers of GM damage, and different software packages have been developed or optimized for measuring it in MS. FreeSurfer software (http://surfer.nmr.mgh.harvard.edu)^3,4 allows automatic calculation of cortical thickness and the volume of subcortical GM structures by using 3D T1-weighted images. Briefly, the image-processing pipeline includes Talairach transformation of the 3D T1-weighted images and segmentation of the subcortical white matter and deep GM structures, relying on the gray and white matter boundaries and pial surfaces. The FMRIB Integrated Registration and Segmentation Tool (FIRST; http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FIRST) software package⁵ automatically segments subcortical GM structures also on the basis of 3D T1-weighted images. Briefly, FIRST is a model-based segmentation and registration program that uses shape and appearance models constructed from manually segmented images. On the basis of the learned models, FIRST searches through linear combinations of shape modes of variation for the most probable shape instance, given the observed intensities in the 3D T1-weighted input images. Both software packages have been shown to be accurate and reproducible.^6–11The study of cortical pathology in patients with MS by using FreeSurfer has shown cortical thinning in patients with MS compared with healthy controls,^12,13 which has been related to lesion volume, disease duration, disability,¹² and cognitive impairment.¹⁴ Also, cortical thinning of the superior frontal gyrus, thalamus, and cerebellum significantly predicted conversion to MS in patients presenting with clinically isolated syndromes,¹⁵ and global cortical thinning for 6 years was significantly associated with a more aggressive disease evolution.¹⁶ The volume of deep GM structures (measured with both FreeSurfer and FIRST) has also been shown to be lower in patients with MS compared with healthy controls,^17–19 and it has been related to different clinical disease outcomes such as fatigue,²⁰ cognitive impairment,^17–19,21 disability,¹⁹ and walking function.²²Both FreeSurfer and FIRST have been optimized for 3D T1-weighted gradient-echo images that incorporate a magnetization-prepared inversion pulse that increases the T1-weighting.²³ Unfortunately, for most of the historical MS cohorts with long-term clinical and radiologic follow-up, only 2D spin-echo (2D-SE) T1-weighted images were acquired, a sequence that does not provide an optimal contrast between gray and white matter, particularly when acquired with high-field magnets.²⁴ The objectives of this work were the following: 1) to evaluate whether cortical thickness and subcortical volumes obtained with FreeSurfer could be reliably measured with 2D-SE T1-weighted images by using as the criterion standard the same measures obtained with 3D gradient-echo (3D-GE) T1-weighted sequences, 2) to investigate whether subcortical volumes obtained with FIRST could be reliably measured in 2D-SE T1-weighted images by using as the criterion standard the same measures obtained with 3D-GE T1-weighted images, and 3) to assess whether the correlations between clinical outcomes and subcortical normalized volumes obtained with 3D-GE and 2D-SE T1-weighted images had a similar strength and direction.     

Evaluation of aqueductal stenosis by 3D sampling perfection with application-optimized contrasts using different flip angle evolutions sequence: preliminary results with 3T MR imaging

BACKGROUND AND PURPOSE:Diagnosis of AS and periaqueductal abnormalities by routine MR imaging sequences is challenging for neuroradiologists. The aim of our study was to evaluate the utility of the 3D-SPACE sequence with VFAM in patients with suspected AS.MATERIALS AND METHODS:PC-MRI and 3D-SPACE images were obtained in 21 patients who had hydrocephalus on routine MR imaging scans and had clinical suspicion of AS, as well as in 12 control subjects. Aqueductal patency was visually scored (grade 0, normal; grade 1, partial obstruction; grade 2, complete stenosis) by 2 experienced radiologists on PC-MRI (plus routine T1-weighted and T2-weighted images) and 3D-SPACE images. Two separate scores were statistically compared with each other as well as with the consensus scores obtained from general agreement of both radiologists.RESULTS:There was an excellent correlation between 3D-SPACE and PC-MRI scores (κ = 0.828). The correlation between 3D-SPACE scorings and consensus-based scorings was higher compared with the correlation between PC-MRI and consensus-based scorings (r = 1, P < .001 and r = 0.966, P < .001, respectively).CONCLUSIONS:3D-SPACE sequence with VFAM alone can be used for adequate and successful evaluation of the aqueductal patency without the need for additional sequences and examinations. Noninvasive evaluation of the whole cranium is possible in a short time with high resolution by using 3D-SPACE.

AS is the most common cause of the obstructive hydrocephalus.¹ The etiology of AS is frequently idiopathic, but in some patients, X-linked recessive inheritance has been reported.^2,3 Webbing, adhesion, or aqueductal forking can be listed among etiologic factors of primary non-neoplastic AS.⁴ Periaqueductal lesions (such as cysts, tumors, infections) can lead to aqueductal stenosis as well.^2,3 There is no worldwide accepted MR imaging protocol for the evaluation of patients with a preliminary diagnosis of AS; hence, it is usually difficult to clearly define the etiology of hydrocephalus by using routine MR images.^3,5 Moreover, invasive techniques (ie, contrast-enhanced cisternography and/or ventriculographic studies) are required for an accurate diagnosis, and this requirement can easily delay the patient management, increase the cost, and lead to serious complications including death.^3,6In most patients, MR imaging plays a pivotal role in planning the surgical procedure (such as ventriculoperitoneal shunt, endoscopic third ventriculostomy, or endoscopic aquaductoplasty).^3,6,7 With the advent of 3T MR imaging systems, there has been a marked increase in the SNR of images, resulting in improvement of the image quality and spatial resolution and shortening of the scanning times.⁸ On the other hand, the main disadvantage of 3T MR imaging systems is their high SAR, which could be eliminated by recently developed approaches such as the 3D-SPACE technique.^9,10 Moreover, using a different flip angle–mode technique at 3T can provide 3D images that can evaluate the whole cranium by shortening the acquisition time.⁸ T1-weighted, proton-density weighted, FLAIR, conventional, and/or heavily T2-weighted MR images can be obtained with a high SNR value in a short time and with a low specific absorption rate value with 3D-SPACE.¹⁰ Isotropic 3D acquisitions with high spatial resolution have an important advantage for the evaluation of intracranial complex structures.^11,12Our previous experience in animal studies with VFAM instead of a constant flip angle mode in T2-weighted 3D-SPACE sequences revealed a better assessment of CSF flow dynamics as well as a better understanding of the aqueductal patency and definition of the accompanying abnormalities.¹³ Our aim in this prospective study was to evaluate the efficacy of T2-weighted 3D-SPACE with VFAM acquisition in the evaluation of aqueductal patency on a 3T MR imaging system. To the best of our knowledge, there is no previous report in the literature regarding the role of this new sequence in the assessment of aqueductal patency as well as in obstructive hydrocephalus.     

Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions

BACKGROUND AND PURPOSE:The development of new MR imaging scanners with stronger gradients and improvement in coil technology, allied with emerging fast imaging techniques, has allowed a substantial reduction in MR imaging scan times. Our goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with the standard clinical protocol.MATERIALS AND METHODS:Fifty-three patients referred for brain MR imaging with contrast were scanned with a 3T scanner. Each MR image consisted of 5 basic fast precontrast sequences plus standard and accelerated versions of the same postcontrast T1WI sequences. Two neuroradiologists assessed the image quality and the final diagnosis for each set of postcontrast sequences and compared their performances.RESULTS:The acquisition time of the combined accelerated pre- and postcontrast sequences was 10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and 36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI had fewer image artifacts (P < .001) and better overall diagnostic quality (P < .001). Although the 10-minute MPRAGE sequence showed a tendency to have more artifacts than the standard sequence (P = .08), the overall diagnostic quality was similar (P = .66). Moreover, there was no statistically significant difference in the diagnostic performance between the protocols. The sensitivity, specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%, and 98.1%.CONCLUSIONS:The 10-minute brain MR imaging protocol with contrast is comparable in diagnostic performance with the standard protocol in an inpatient motion-prone population, with the additional benefits of reducing acquisition times and image artifacts.

The prolonged acquisition time of MR imaging is uncomfortable for patients, introduces the potential for motion-related artifacts (especially in critically ill patients), limits clinical availability, and increases cost. Consequently, in the past decade, there has been a concerted effort to develop fast and ultrafast MR imaging protocols.^1–7For many years, continual development of new scanners with stronger gradients and the improvement of coil technology,^8–10 allied with a number of emerging fast imaging techniques, has allowed substantial reduction in MR imaging scan times.^1,11–13 More recently, the development of parallel imaging, a robust method for accelerating MR imaging data acquisitions based on obtaining simultaneous information from arrays of coils, allowing decreased filling of k-space lines, has been the preferred method for decreasing acquisition times.^14–16This study is in accord with recent effort within the neuroradiology research community to accelerate the clinical MR imaging studies and expands on a 5-minute noncontrast brain MR imaging protocol previously validated by our group.¹¹ We previously demonstrated similar image quality and diagnostic accuracy of a 5-minute brain MR imaging protocol compared with the conventional protocol in a motion-prone clinical population. The aim of this study was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with a standard clinical protocol in a similar clinical population.     

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy

BACKGROUND AND PURPOSE:Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy.MATERIALS AND METHODS:Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping–oxygen extraction fraction images.RESULTS:Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping–oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5–249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping–oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively.CONCLUSIONS:Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.

Cerebral hyperperfusion following carotid endarterectomy (CEA) has been defined as a substantial increase in ipsilateral cerebral blood flow well above the metabolic demands of brain tissue following surgical repair of carotid stenosis.^1,2 Cerebral hyperperfusion syndrome after CEA is a complication of cerebral hyperperfusion;³ its characteristic features include unilateral headache, pain in the face or eyes, seizures, and focal symptoms secondary to intracerebral hemorrhage or cerebral edema.^1–4 Intracerebral hemorrhage has a low incidence (1%), but patients with this condition have a poor prognosis.⁵ Moreover, several studies have found that post-CEA hyperperfusion, even when asymptomatic, causes slight but diffuse damage to the ipsilateral cerebral cortex and white matter.^3,6,7 This damage that occurs after CEA hyperperfusion is a principal cause of the postoperative cognitive impairment observed in 10% of patients following CEA.^3,6,7Cerebrovascular autoregulatory mechanisms operate through dilation of precapillary resistance vessels that maintain CBF when reductions in cerebral perfusion pressure occur, and this is referred to as stage 1 ischemia.^3,8–10 However, the autoregulatory mechanism provides insufficient compensation for severe decreases in cerebral perfusion pressure, which then leads to decreased CBF, referred to as misery perfusion or stage 2 ischemia.^3,8–10 Thus, misery perfusion, which is defined as marginally sufficient cerebral blood supply relative to cerebral metabolic demand, is a situation with severely impaired cerebral hemodynamics.⁸ This condition occurs in patients with chronic steno-occlusive diseases of the internal carotid artery.⁸The risk factors for cerebral hyperperfusion include high-grade stenosis, poor collateral blood flow, contralateral carotid occlusion, and long-standing hypertension, and they often result in impaired cerebral hemodynamics.^11–14 When normal perfusion pressure is rapidly restored after CEA, hyperperfusion may occur in regions of the brain with impaired autoregulation due to chronic ischemia. This hypothesis is like the “normal perfusion pressure breakthrough” theory of Spetzler et al.^13,15 Indeed, preoperative misery perfusion in the affected cerebral hemisphere is reportedly associated with the development of cerebral hyperperfusion following CEA or carotid stent placement for cervical ICA stenosis.^16,17Misery perfusion is principally detected as an increased oxygen extraction fraction (OEF) on positron-emission tomography.⁸ Several approaches have been attempted to measure OEF by using MR imaging techniques.¹⁸ In general, these techniques use blood oxygen level–dependent effects induced by differences in magnetic susceptibility between oxy- and deoxyhemoglobin to quantify oxygenation in venous structures and/or brain parenchyma.^19–21 Quantitative susceptibility mapping (QSM) is a postprocessing technique for quantifying the magnetic susceptibility of venous structures and brain parenchyma from T2*-weighted magnitude/phase images, which can be easily obtained by commercial scanners.²² Indeed, a recent study has introduced an OEF measurement method based on the QSM technique and has demonstrated that cerebral OEF images generated from QSM at 7T MR imaging correlate with OEF images on PET and provide high sensitivity and high specificity for detecting misery perfusion in the middle cerebral artery territory in patients with unilateral chronic ICA or MCA steno-occlusive disease.²³The purpose of the present study was to determine whether preoperative OEF imaging generated from 7T MR QSM could identify patients at risk for cerebral hyperperfusion following CEA.     

Brain Parenchymal Signal Abnormalities Associated with Developmental Venous Anomalies in Children and Young Adults

BACKGROUND AND PURPOSE:Abnormal signal in the drainage territory of developmental venous anomalies has been well described in adults but has been incompletely investigated in children. This study was performed to evaluate the prevalence of brain parenchymal abnormalities subjacent to developmental venous anomalies in children and young adults, correlating with subject age and developmental venous anomaly morphology and location.MATERIALS AND METHODS:Two hundred eighty-five patients with developmental venous anomalies identified on brain MR imaging with contrast, performed from November 2008 through November 2012, composed the study group. Data were collected for the following explanatory variables: subject demographics, developmental venous anomaly location, morphology, and associated parenchymal abnormalities. Associations between these variables and the presence of parenchymal signal abnormalities (response variable) were then determined.RESULTS:Of the 285 subjects identified, 172 met inclusion criteria, and among these subjects, 193 developmental venous anomalies were identified. Twenty-six (13.5%) of the 193 developmental venous anomalies had associated signal-intensity abnormalities in their drainage territory. After excluding developmental venous anomalies with coexisting cavernous malformations, we obtained an adjusted prevalence of 21/181 (11.6%) for associated signal-intensity abnormalities in developmental venous anomalies. Signal-intensity abnormalities were independently associated with younger subject age, cavernous malformations, parenchymal atrophy, and deep venous drainage of developmental venous anomalies.CONCLUSIONS:Signal-intensity abnormalities detectable by standard clinical MR images were identified in 11.6% of consecutively identified developmental venous anomalies. Signal abnormalities are more common in developmental venous anomalies with deep venous drainage, associated cavernous malformation and parenchymal atrophy, and younger subject age. The pathophysiology of these signal-intensity abnormalities remains unclear but may represent effects of delayed myelination and/or alterations in venous flow within the developmental venous anomaly drainage territory.

Developmental venous anomalies (DVAs) are frequently identified on routine MR imaging of the brain with contrast. DVAs are typically considered normal variants of venous development and usually have no associated imaging findings. However, a subset of DVAs has been associated with findings such as cavernous malformations (CMs),^1–3 thrombosis with subsequent venous infarction,^4–8 lobar atrophy,⁹ T2 and FLAIR signal-intensity abnormalities,^9,10 and SWI hypointensities.¹¹ Signal abnormalities can occur in the drainage territory of DVAs and may produce diagnostic uncertainty with regard to the significance and relationship to presenting symptoms. Signal abnormalities on MR imaging have been described in 12.5%¹⁰ to 28.3%⁹ of DVAs in adults, with an increasing prevalence with older age. While well described in adults, this relationship has not been investigated in children, to our knowledge. The MR imaging appearance of the brain in children is quite different from that in adults during myelination, and the effect of DVAs on regional brain maturation has not been studied.The most commonly proposed etiologies for parenchymal abnormalities associated with DVAs are chronic venous hypertension/insufficiency leading to ischemia or microhemorrhage.^9–12 Although the effect of brain maturation is unknown, on the basis of these pathophysiologic mechanisms, we hypothesized that parenchymal abnormalities would be less common in children compared with adults. This study was performed to test this hypothesis and to investigate clinical factors and DVA characteristics associated with parenchymal signal abnormalities in children and young adults.     

Quantitative Intracranial Atherosclerotic Plaque Characterization at 7T MRI: An Ex Vivo Study with Histologic Validation

BACKGROUND AND PURPOSE:In recent years, several high-resolution vessel wall MR imaging techniques have emerged for the characterization of intracranial atherosclerotic vessel wall lesions in vivo. However, a thorough validation of MR imaging results of intracranial plaques with histopathology is still lacking. The aim of this study was to characterize atherosclerotic plaque components in a quantitative manner by obtaining the MR signal characteristics (T1, T2, T2*, and proton density) at 7T in ex vivo circle of Willis specimens and using histopathology for validation.MATERIALS AND METHODS:A multiparametric ultra-high-resolution quantitative MR imaging protocol was performed at 7T to identify the MR signal characteristics of different intracranial atherosclerotic plaque components, and using histopathology for validation. In total, 38 advanced plaques were matched between MR imaging and histology, and ROI analysis was performed on the identified tissue components.RESULTS:Mean T1, T2, and T2* relaxation times and proton density values were significantly different between different tissue components. The quantitative T1 map showed the most differences among individual tissue components of intracranial plaques with significant differences in T1 values between lipid accumulation (T1 = 838 ± 167 ms), fibrous tissue (T1 = 583 ± 161 ms), fibrous cap (T1 = 481 ± 98 ms), calcifications (T1 = 314 ± 39 ms), and the intracranial arterial vessel wall (T1 = 436 ± 122 ms).CONCLUSIONS:Different tissue components of advanced intracranial plaques have distinguishable imaging characteristics with ultra-high-resolution quantitative MR imaging at 7T. Based on this study, the most promising method for distinguishing intracranial plaque components is T1-weighted imaging.

Ischemic stroke is one of the major diseases in the Western world, associated with high morbidity and mortality.^1,2 Identifying the cause of ischemic stroke is of great clinical importance, not only for deciding the best treatment options for the individual patient but also for possibly preventing future ischemic events, both recurrent and new.Intracranial atherosclerosis is one of the main causes of ischemic stroke and TIA worldwide, accounting for approximately 9%–33% of all ischemic strokes and TIAs (depending on race-ethnicity) and is the major cause of cerebral ischemic events in the Asian population. Additionally, the risk of recurrent ischemic stroke is increased in patients with underlying intracranial atherosclerosis.^3–8 Similar to extracranial atherosclerosis, for intracranial atherosclerosis, the degree of luminal stenosis is currently the main factor determining whether an atherosclerotic plaque is symptomatic and/or treatment is necessary. In the past decade, plaque composition has become an additional important feature in extracranial atherosclerosis management, enabling identification of specific culprit lesions requiring treatment, even when not causing significant stenosis.^9–12 However, for intracranial atherosclerosis, this is not yet common practice, even though the literature suggests that also intracranially, stenosis grade is not always associated with a risk of ischemic events: In patients with a high-grade stenosis, only 1 in every 5–10 patients will have a recurrent ischemic stroke.^5,6,13,14 This implies that like in extracranial atherosclerosis, luminal information is not the only important marker for future cerebrovascular events.In recent years, several high-resolution intracranial vessel wall imaging techniques using 3T and 7T MR imaging have emerged for the evaluation and characterization of atherosclerotic vessel wall lesions in vivo.¹⁵ However, these in vivo techniques so far have not been validated with histopathology, due to poor accessibility of the intracranial arteries. Therefore, the question arises if these techniques are truly able—ie, have enough image contrast—to distinguish different atherosclerotic plaque components. In the past 2 years, 2 ex vivo correlation studies have been performed at 7T MR imaging to assess its ability to visualize different intracranial atherosclerotic plaque components.^16,17 These ex vivo studies showed that 7T MR imaging is capable of identifying focal thickening of the intracranial arterial vessel wall and distinguishing different plaque components within advanced intracranial atherosclerotic plaques with different image contrast weightings. Recently, a first case report was published demonstrating the correlation between certain intracranial atherosclerotic plaque components visualized in vivo at 3T and histologic validation of the plaque postmortem.¹⁸ Those studies used qualitative MR images to score the atherosclerotic plaque signal heterogeneities. As a next step toward validation, quantitative assessment of MR signal characteristics of specific plaque components might enable more firm conclusions regarding the ability of T1-, T2-, T2*-, and proton density (PD)-weighted sequences in characterizing intracranial atherosclerotic plaques. Once it is known which plaque components can be identified with ex vivo MR imaging sequences, a translation can be made to in vivo intracranial vessel wall MR imaging, by developing sequences based on the nuclear magnetic resonance tissue properties of the identified atherosclerotic plaque components. In the current study, a multiparametric ultra-high-resolution quantitative MR imaging protocol was performed to identify the MR signal characteristics of different intracranial atherosclerotic plaque components, and using histopathology for validation.