Temporal and Spatial Variances in Arterial Spin-Labeling Are Inversely Related to Large-Artery Blood Velocity

BACKGROUND AND PURPOSE:The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling–CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations.MATERIALS AND METHODS:We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20–88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation.RESULTS:Large-artery blood velocity was inversely associated with labeling efficiency (P = .007), temporal SNR (P < .001), and spatial coefficient of variation (P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency.CONCLUSIONS:Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification.

Quantitative CBF is a valuable measure to track pathophysiologic changes in cerebrovascular function and brain metabolism.¹ Two noninvasive MR imaging–based techniques, which capture distinct hemodynamic features, are arterial spin-labeling (ASL) and phase-contrast (PC) imaging. ASL measures regional CBF with tissue-level precision, using magnetized arterial blood water as an endogenous tracer.^2,3 PC imaging, by comparison, quantifies whole-brain CBF with a bipolar gradient to induce phase shifts proportional to blood velocity within the carotid and vertebral arteries.⁴ Among the factors that influence ASL, CBF quantification is most sensitive to labeling efficiency and the equilibrium magnetization of arterial blood.⁵ In practice, labeling efficiency is assumed constant (eg, 0.85).³ Field inhomogeneity⁶ and nonlinear effects of blood velocity,^7–9 however, contribute individual variability. Studies that have empirically estimated labeling efficiency by normalizing pseudocontinuous ASL-based whole-brain CBF to that measured with PC imaging report individual labeling efficiencies ranging from 0.7 to 1.1.^8,10 Recent work in a large middle-aged cohort, however, has questioned the validity of this normalization method due to substantial variability within individual measurements.¹¹ Rather than incorporating PC-based CBF as a normalization factor, corresponding knowledge of PC-based metrics, such as blood velocity, may be beneficial for planning ASL protocols because many labeling and acquisition parameters are timing-based.Simulated and empiric ASL data suggest that labeling efficiency is highest for blood velocities of ∼10 cm/s.⁸ These studies reflect hemodynamics in healthy adults, leaving questions regarding the reliability of ASL in patients with vascular pathology. Aging, cerebrovascular risk factors, and stroke status are associated with larger cross-sectional areas and slower, more pulsatile blood velocity within the large arteries.^12,13 Such changes occurring in proximity to the ASL labeling plane may confound CBF quantification in these clinical cohorts. For instance, age is associated with a decreased signal-to-noise ratio, due, in part, to increased variance between individual control-tag difference images.¹⁴ Arterial transit time is another velocity-sensitive hemodynamic characteristic associated with aging¹⁵ and the presence of white matter hyperintensities (WMH).¹⁶ Prolonged transit time is visualized by localized regions of hyperintense ASL signal, contributing to greater spatial variance in whole-brain CBF.¹⁷ To expand our understanding of the relationship between large-artery characteristics and CBF estimates, we compared ASL and PC in individuals across a range of age and vascular pathology. We hypothesized that large-artery blood velocity would be inversely related to labeling efficiency, temporal SNR, and spatial variance in ASL.     

Diagnostic Accuracy of Screening Arterial Spin-Labeling MRI Using Hadamard Encoding for the Detection of Reduced CBF in Adult Patients with Ischemic Moyamoya Disease

BACKGROUND AND PURPOSE:Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients.MATERIALS AND METHODS:Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated.RESULTS:The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays–CBF ratios (0.885) than for the standard postlabeling delay–CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays–CBF ratios were 100% (95% confidence interval, 100%–100%) and significantly higher than the sensitivity (95% CI, 44%–80%) and negative predictive value (95% CI, 88%–97%) for the standard postlabeling delay–CBF ratio, respectively.CONCLUSIONS:ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease of unknown etiology that is characterized by bilateral steno-occlusive changes in the terminal portion of the ICA and an abnormal vascular network at the base of the brain.^1,2 The typical treatment for patients with ischemia symptoms is revascularization surgery, which can involve anastomosis of the superficial temporal artery and MCA.³ Regardless of the severity of cerebral ischemia, this procedure is universally recommended for pediatric patients with MMD with ischemic symptoms because in such cases, the brain is still developing.^3-5 By contrast, revascularization surgery is selectively recommended for adult patients presenting with ischemic symptoms.^3,6 However, no clear guidelines are available for this selection. Two recent studies used PET and brain perfusion SPECT to measure the oxygen extraction fraction and CBF, respectively, and demonstrated that among adult patients (older than 30 but younger than 60 years of age) receiving medication alone for symptomatic ischemic MMD without hemodynamic compromise, such as misery perfusion or reduced CBF, the incidence of recurrent ischemic events was very low (approximately 1% per year).^7,8 Moreover, the recurrent ischemic episodes were transient ischemic attacks only, and no changes were seen in scores on the modified Rankin Disability Scale after the recurrence of ischemic symptoms in such patients.⁷ In addition, neither cerebral hemodynamics nor cognitive function had deteriorated at 2 years after the last event in patients without recurrent ischemic events.⁷ Initial treatment with medication alone may be recommended for adult patients with ischemic MMD without hemodynamic compromise,⁷ and the determination of whether hemodynamic compromise exists in the symptomatic cerebral hemisphere is important for the management of such patients.^7,8 However, the clinical use of PET or brain perfusion SPECT to detect misery perfusion or reduced CBF is precluded by its high cost and limited availability in the clinical setting. Other screening modalities for detecting hemodynamic compromise before performing PET or brain perfusion SPECT would therefore be useful.Arterial spin-labeling (ASL) MR imaging is a noninvasive technique that can quantify CBF.^9-11 A number of studies involving patients with MMD conducted using ASL MR imaging with a single postlabeling delay (PLD) have simply compared CBF measured using ASL MR imaging with brain perfusion parameters measured using other modalities such as PET, SPECT, and dynamic susceptibility contrast perfusion MR imaging.^12-14 However, almost all the cerebral cortical regions in MMD have some degree of perfusion delay, which varies even within individual cerebral cortical regions of a single patient.¹⁵ Therefore, it is difficult to obtain precise CBF measurements using the standard ASL method with a single PLD in MMD.¹⁵ By contrast, theoretically, ASL measurements covering a wide range of PLD times can be interpreted to estimate CBF with practical spatial and temporal resolutions in the clinical setting.^16,17 Actually, multi-PLD ASL MR imaging with corrections using the arterial transit time (ATT) significantly improved CBF quantification compared with single-PLD ASL MR imaging.^18,19 However, the accuracy of multi-PLD ASL MR imaging for detecting hemodynamic compromise has not been reported. Hadamard-encoding techniques have recently been applied to the ASL methods to calculate the ASL signals as multiple PLDs by dividing the ASL signal into sub-boluses of different PLDs.¹⁶ Several investigations have demonstrated that Hadamard-encoded labeling strategies for healthy human subjects provide robust CBF measurements in a time-efficient manner with shorter scan times (<10 minutes).²⁰ This benefit may be suitable for the detection of reduced CBF in patients with MMD.Given this background, the aims of this study were to determine the diagnostic accuracy of ASL MR imaging using Hadamard-encoded multiple PLDs for the detection of reduced CBF, a key determinant for revascularization surgery, in adult patients with ischemic MMD, and to propose practical clinical algorithms using ASL MR imaging and subsequent management in such patients.     

Noninvasive Evaluation of CBF and Perfusion Delay of Moyamoya Disease Using Arterial Spin-Labeling MRI with Multiple Postlabeling Delays: Comparison with 15O-Gas PET and DSC-MRI

BACKGROUND AND PURPOSE:Arterial spin-labeling MR imaging with multiple postlabeling delays has a potential to evaluate various hemodynamic parameters. To clarify whether arterial spin-labeling MR imaging can identify CBF and perfusion delay in patients with Moyamoya disease, we compared arterial spin-labeling, DSC, and ¹⁵O-gas PET in terms of their ability to identify these parameters.MATERIALS AND METHODS:Eighteen patients with Moyamoya disease (5 men, 13 women; ages, 21–55 years) were retrospectively analyzed. CBF values of pulsed continuous arterial spin-labeling using 2 postlabeling delays (short arterial spin-labeling, 1525 ms; delayed arterial spin-labeling, 2525 ms) were compared with CBF values measured by ¹⁵O-gas PET. All plots were divided into 2 groups by the cutoff of time-based parameters (the time of the maximum observed concentration, TTP, MTT, delay of MTT to cerebellum, and disease severity [symptomatic or not]). The ratio of 2 arterial spin-labeling CBFs (delayed arterial spin-labeling CBF to short arterial spin-labeling CBF) was compared with time-based parameters: time of the maximum observed concentration, TTP, and MTT.RESULTS:The short arterial spin-labeling–CBF values were significantly correlated with the PET-CBF values (r = 0.63; P = .01). However, the short arterial spin-labeling–CBF value dropped in the regions with severe perfusion delay. The delayed arterial spin-labeling CBF overestimated PET-CBF regardless of the degree of perfusion delay. Delayed arterial spin-labeling CBF/short arterial spin-labeling CBF was well correlated with the time of the maximum observed concentration, TTP, and MTT (ρ = 0.71, 0.64, and 0.47, respectively).CONCLUSIONS:Arterial spin-labeling using 2 postlabeling delays may detect PET-measured true CBF and perfusion delay in patients with Moyamoya disease. Provided its theoretic basis and limitations are considered, noninvasive arterial spin-labeling could be a useful alternative for evaluating the hemodynamics of Moyamoya disease.

Moyamoya disease is a slowly progressive cerebrovascular disease with occlusion of the terminal portion of the internal carotid arteries.^1–3 Perfusion studies are indispensable for determining the most appropriate treatment strategy for individual patients with this disease because the hemodynamic conditions are highly variable among patients.⁴ Another characteristic of Moyamoya disease is its prevalence among children and adolescents, which underscores the need for truly noninvasive studies.To understand the hemodynamic status of patients with Moyamoya disease, it is important to evaluate CBF and various time-based parameters. ¹⁵O-gas PET provides quantitative CBF values by using a diffusible tracer and calculations by the Kety–Schmidt equation, and thus is considered a criterion standard technique. However, the procedure is costly and not readily available at most institutes, and the radiation exposure makes it difficult to apply this technique repeatedly for young or juvenile patients. In contrast, DSC is free of ionized radiation, easily available at most institutes, and can calculate time-based parameters such as the time of the maximum observed concentration (Tmax), TTP, and MTT, which have been reported to be important clinical biomarkers in Moyamoya disease.^5–7 Nevertheless, DSC still requires an injection of contrast media.Arterial spin-labeling MR imaging (ASL) has emerged as a noninvasive technique for evaluating cerebral hemodynamics^8–11 because it uses magnetically labeled water as an endogenous tracer. For the quantitation of CBF, ASL uses a mechanism similar to that of PET. The main problem with the ASL technique is its inferior SNR, but the recent spread of high-magnetic-field clinical MR imaging systems has made this method applicable in many clinical centers, providing high-quality CBF images. ASL has been applied to various fields,^12–14 and several studies have reported a correlation between ASL-CBF and PET-CBF in healthy subjects, patients with Alzheimer disease, patients with occlusive atherosclerotic cerebrovascular disease, and children with Moyamoya disease.^15–20 ASL with multiple postlabeling delays (PLDs) may also be used to evaluate time-based parameters and angiographic collateral flows, as suggested in some studies of symptomatic atherosclerotic cerebrovascular disease.^21–23We considered that noninvasive ASL could be appropriate for the clinical management of Moyamoya disease and that ASL might detect CBF and perfusion delay of the patients. Numerous ASL studies have been conducted in patients with Moyamoya disease,^20,24–31 but studies simultaneously comparing ASL with both ¹⁵O-gas PET and time-based parameters of DSC are quite rare. In the present study, to verify the proposed usefulness of ASL, we compared ASL-CBF values obtained when using 2 PLDs with the data obtained by DSC and ¹⁵O-gas PET in patients with Moyamoya disease.     

CT perfusion quantification of small-vessel ischemic severity

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) abnormalities are previously demonstrated in white matter disease. A gradation of change may exist between patients with mild and more severe white matter disease. An association between blood brain barrier dysfunction, increasing age and white matter disease is also suggested. The purpose of this study was to quantify and correlate white matter disease severity and CT perfusion (CTP)-derived CBF and to determine whether permeability surface abnormality increases with white matter disease severity.MATERIALS AND METHODS: One hundred twenty patients with strokelike symptoms underwent CTP and MR imaging. Of these, 35 patients (15 women, 20 men; age, 66 ± 15.7 years) with rapidly resolving symptoms and normal imaging characteristics consistent with transient ischemic attack were retrospectively reviewed and constituted the study cohort. Two blinded neurologists rated white matter severity, assigning age-related white matter change (ARWMC) scores. Patients were dichotomized a priori into mild and moderate-to-severe. CBF, cerebral blood volume (CBV), mean transit time (MTT), and permeability surface product maps were calculated for periventricular and subcortical white matter regions and average white and gray matter. Associations with white matter severity were tested by uni- and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed.RESULTS: White matter disease was mild in 26 patients and moderate-to-severe in 9. Age was associated with increased likelihood of having moderate-to-severe white matter disease (P = .02). ARWMC correlated with subcortical (r = −0.50, P < .001) and average CBF (r = −0.55, P < .001). White matter severity was associated with subcortical (P = .03) and average (P = .03) white matter CBF, with a trend toward periventricular white matter CBF (P = .05). Uni- and multivariate analysis controlling for the confounding effect of age demonstrated significant association between white matter severity and subcortical (P = .032) white matter CBF. Area under the curve was 0.82. No permeability surface abnormality was found.CONCLUSIONS: CTP-derived subcortical white matter CBF is independently associated with white matter disease severity.

White matter changes are frequent in patients with vascular risk factors, cerebrovascular disease, and cognitive impairment.¹ The pathogenesis is poorly understood. Various histopathologic correlates have been described, including loss of ependyma with gliosis, glial swelling, demyelination, dilated perivascular spaces, lacunar infarcts, spongiosis, arteriolar hyalinosis, amyloid angiopathy, and cyst formation.^2–4 A vascular etiology is strongly suggested, given the frequent association with increasing age, hypertension, stroke, and markers of cellular ischemia, including hypoxia inducible factor, neuroglobulin, and matrix metalloproteinase protein MMP7.^5–7 Other associations include arteriosclerosis,⁸ impaired cerebral autoregulation, hypoperfusion, CSF flow disturbances, and blood-brain barrier (BBB) disruption.^7,9Several validated white matter rating scales allow visual quantification of disease burden on CT or MR imaging. The age-related white matter change (ARWMC) scale can be applied to both CT and MR imaging changes and has been recommended in an attempt to standardize nomenclature in vascular cognitive impairment imaging.¹⁰ White matter lesion visualization is, however, reduced on CT compared with MR imaging. Additionally, visual rating score performances are imperfect and are limited by a ceiling effect. The wide variation in lesion extent with high visual scores results in a lower correlation with clinical symptoms. Whether techniques that provide estimation of white matter hemodynamic parameters independent of CT or MR imaging lesion visualization would better assess severity is unknown but potentially may circumvent these problems.Cerebral blood flow (CBF) abnormalities were previously demonstrated in white matter disease by xenon CT (Xe-CT),¹¹ positron-emission tomography (PET),¹² and MR imaging.^13,14 Correlation of XeCT and single-photon emission tomography (SPECT) hypoperfusion with leukoaraiosis severity was previously described.^11,15 Recent data suggest that hemodynamic alterations precede white matter change.¹⁶ An association between BBB dysfunction, increasing age, dementia, and white matter disease is suggested, with parenchymal gadolinium-diethylene-triamine pentaacetic acid leakage shown in elderly patients with diabetes.¹⁷ Furthermore, microvascular changes, BBB dysfunction, and microglial and astroglial cell activation are reported in primates with cognitive decline.¹⁸ Progress in cross-sectional CT imaging technology allows quantification of absolute cerebral hemodynamic parameters with greater resolution than MR imaging or SPECT-based techniques. CT perfusion (CTP) is cheaper, faster, and more widely available than MR imaging, SPECT, or Xe-CT techniques. CTP is widely used in the evaluation of patients with stroke, but no previous study has examined the relationship between CTP-derived hemodynamic variables and white matter disease severity. The purpose of this study was to test the ability of CTP-derived hemodynamic parameters, including CBF, cerebral blood volume (CBV), mean transit time (MTT), and BBB permeability surface product to quantify white matter disease severity. Our hypothesis was that CTP-derived hemodynamic parameters and, in particular, CBF correlate with and may be used to quantify white matter disease severity. Furthermore, we hypothesized that permeability surface is expected to increase with greater white matter disease severity.     

3D Pseudocontinuous Arterial Spin-Labeling MR Imaging in the Preoperative Evaluation of Gliomas

BACKGROUND AND PURPOSE:Previous studies showed conflicting results concerning the value of CBF maps obtained from arterial spin-labeling MR imaging in grading gliomas. This study was performed to investigate the effectiveness of CBF maps derived from 3D pseudocontinuous arterial spin-labeling in preoperatively assessing the grade, cellular proliferation, and prognosis of gliomas.MATERIALS AND METHODS:Fifty-eight patients with pathologically confirmed gliomas underwent preoperative 3D pseudocontinuous arterial spin-labeling. The receiver operating characteristic curves for parameters to distinguish high-grade gliomas from low-grade gliomas were generated. Pearson correlation analysis was used to assess the correlation among parameters. Survival analysis was conducted with Cox regression.RESULTS:Both maximum CBF and maximum relative CBF were significantly higher in high-grade gliomas than in low-grade gliomas (P < .001). The areas under the curve for maximum CBF and maximum relative CBF in distinguishing high-grade gliomas from low-grade gliomas were 0.828 and 0.863, respectively. Both maximum CBF and maximum relative CBF had no correlation with the Ki-67 index in all subjects and had a moderate negative correlation with the Ki-67 index in glioblastomas (r = −0.475, −0.534, respectively). After adjustment for age, a higher maximum CBF (P = .008) and higher maximum relative CBF (P = .005) were associated with worse progression-free survival in gliomas, while a higher maximum relative CBF (P = .033) was associated with better overall survival in glioblastomas.CONCLUSIONS:3D pseudocontinuous arterial spin-labeling–derived CBF maps are effective in preoperative evaluation of gliomas. Although gliomas with a higher blood flow are more malignant, glioblastomas with a lower blood flow are likely to be more aggressive.

Glioma is the most common intracranial malignant tumor, accounting for almost 80% of primary malignant brain tumors.¹ Grading of gliomas is important for an optimal therapy plan and predicting outcome.^2,3 According to the World Health Organization (WHO) criteria, gliomas can be classified into 4 groups: grades I–IV. Grade I and grade II gliomas are considered low-grade gliomas (LGGs), while grade III and grade IV gliomas are regarded as high-grade gliomas (HGGs).Advanced MR imaging techniques, such as MR perfusion, have been shown to be more effective than conventional MR imaging techniques in grading gliomas.^4,5 Dynamic susceptibility contrast perfusion imaging is the reference standard for evaluating tumor perfusion.^6,7 However, this technique relies on the intravenous application of a contrast medium, which is not suitable for patients who are allergic to this medium or who have renal failure.^8,9Arterial spin-labeling (ASL) is a noninvasive MR perfusion imaging technique for obtaining CBF maps. Some previous studies based on pulsed ASL and continuous ASL (CASL) have shown that the ASL-derived CBF maps have potential value in grading gliomas^8,10–15 and predicting their progression.^9,16,17 However, although pseudocontinuous ASL (pCASL) is considered an improved method over pulsed ASL and CASL,^18–20 a recent study reported that pCASL-derived CBF maps failed to accurately grade gliomas.²¹On the other hand, according to many previous studies, gliomas with higher tumor blood flow are commonly more malignant.^8–17 However, a recent study found a positive correlation between proliferation activity and levels of a hypoxia biomarker in glioblastoma (GBM),²² suggesting that GBM with a lower blood flow might be more aggressive. Hence, the correlation between relative CBF and the grade of malignancy might be more complex in gliomas.The purpose of this study was to examine the value of the CBF maps derived from 3D pCASL in preoperatively assessing the grade, cellular proliferation, and prognosis of gliomas. Additionally, we performed a subgroup analysis on patients with GBM.     

Association between cerebral microbleeds on T2*-weighted MR images and recurrent hemorrhagic stroke in patients treated with warfarin following ischemic stroke

BACKGROUND AND PURPOSE: Although accumulating evidence suggests the presence of microbleeds as a risk factor for intracerebral hemorrhage (ICH), little is known about its significance in anticoagulated patients. The aim of this study was to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who had received warfarin following atrial fibrillation–associated cardioembolic infarction.MATERIALS AND METHODS: A total of 87 consecutive patients with acute recurrent stroke, including 15 patients with ICH and 72 patients with cerebral infarction, were enrolled in this study. International normalized ratios (INRs), vascular risk factors, and imaging characteristics, including microbleeds on T2*-weighted MR images and white matter hyperintensity (WMH) on T2-weighted MR images, were compared in the 2 groups.RESULTS: Microbleeds were noted more frequently in patients with ICH than in patients with cerebral infarction (86.7% versus 38.9%, P = .0007). The number of microbleeds was larger in patients with ICH than in patients with cerebral infarction (mean, 8.4 versus 2.1; P = .0001). INR was higher in patients with ICH than in patients with cerebral infarction (mean, 2.2 versus 1.4; P < .0001). The frequency of hypertension was higher in patients with ICH than in patients with cerebral infarction (86.7% versus 45.8%, P = .0039). Multivariate analysis revealed that the presence of cerebral microbleeds (odds ratio, 7.383; 95% confidence interval, 1.052–51.830) was associated with ICH independent of increased INR and hypertension.CONCLUSION: The presence of cerebral microbleeds may be an independent risk factor for warfarin-related ICH, but more study is needed because of strong confounding associations with elevated INR and hypertension.

One of the major complications of warfarin treatment following atrial fibrillation–related cardioembolic infarction is the occurrence of intracerebral hemorrhage (ICH). With advancing age, the incidence of both atrial fibrillation–related cardioembolic infarction and warfarin-related ICH increases.Cerebral microbleeds detected by gradient-echo T2*-weighted MR imaging, which are shown as signal-intensity loss, represent hemosiderin deposit^1,2 and are associated with occurrence of ICH.^3–19 Although accumulating evidence suggests that the presence of microbleeds is a risk factor for ICH in patients treated by antiplatelet therapy^13,20 and hemorrhagic complications of anticoagulation in patients with prior ICH and atrial fibrillation have been reported,²¹ little is known about the significance of microbleeds in anticoagulated patients because, to our knowledge, no studies have focused on the association between cerebral microbleeds and anticoagulation therapy in a large number of patients. On the other hand, previous studies focusing on radiographic characteristics have shown that the presence of microangiopathy (leukoaraiosis) detected by CT is a risk factor for warfarin-related ICH.²² However, considering the close association between cerebral microbleeds and leukoaraiosis (white matter hyperintensity [WMH]),^{7,8,11,14–16,19,23,24} one could hypothesize that cerebral microbleeds, which represent bleeding from small vessels, may be more closely associated with ICH than WMH is. Therefore, the present study was performed to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who have received warfarin treatment following atrial fibrillation–associated cardioembolic infarction.     

Anoxic injury-associated cerebral hyperperfusion identified with arterial spin-labeled MR imaging

BACKGROUND AND PURPOSE: Anoxic brain injury is a devastating result of prolonged hypoxia. The goal of this study was to use arterial spin-labeling (ASL) to characterize the perfusion patterns encountered after anoxic injury to the brain.MATERIALS AND METHODS: Sixteen patients with a history of anoxic or hypoxic-ischemic injury ranging in age from 1.5 to 78.0 years (mean, 50.3 years) were analyzed with conventional MR imaging and pulsed ASL 1.0–13.0 days (mean, 4.6 days) after anoxic insult. The cerebral perfusion in each case was quantified by using pulsed ASL as part of the standard stroke protocol. Correlation was made among perfusion imaging, conventional imaging, clinical history, laboratory values, and outcome.RESULTS: Fifteen of the 16 patients showed marked global hyperperfusion, and 1 patient showed unilateral marked hyperperfusion. Mean gray matter (GM) cerebral blood flow (CBF) in these patients was 142.6 mL/100 g of tissue per minute (ranging from 79.9 to 204.4 mL/100 g of tissue per minute). Global GM CBF was significantly higher in anoxic injury subjects, compared with age-matched control groups with and without infarction (F_2,39 = 63.11; P < .001). Three patients had global hyperperfusion sparing areas of acute infarction. Conventional imaging showed characteristic restricted diffusion in the basal ganglia (n = 10) and cortex (n = 13). Most patients examined died (n = 12), with only 4 patients surviving at the 4-month follow-up.CONCLUSION: Pulsed ASL can dramatically demonstrate and quantify the severity of the cerebral hyperperfusion after a global anoxic injury. The global hyperperfusion probably results from loss of autoregulation of cerebral vascular resistance.

Anoxic injuries resulting from global cessation of oxygenated cerebral blood flow (CBF) have profound effects on cerebral metabolism. Characteristic imaging findings include infarctions in regions with higher metabolic demands, including the basal ganglia and cerebral cortex.^1–3 Arterial spin-labeling (ASL) perfusion imaging generates qualitative and quantitative data. ASL perfusion imaging findings in these patients have not been described in the literature. Xenon CT perfusion has been used to evaluate postresuscitation patients with mixed results.^4–6 Other cerebral perfusion methods, such as nuclear medicine hexamethylpropyleneamine oxime single-photon emission CT and O-15 positron-emission tomography (PET), rely on differences in regional perfusion and may not detect a global symmetric hyperperfusion pattern.⁷ The goal of this study was to use ASL to characterize the perfusion patterns encountered after anoxic injury to the brain. We present a series of 16 patients with a history of anoxic injury who demonstrated marked cerebral hyperperfusion on pulsed ASL perfusion imaging. We propose that this marked hyperperfusion is secondary to the loss of autoregulation of cerebral vascular resistance caused by the anoxic injury.     

Arterial spin-labeling MR imaging measurements of timing parameters in patients with a carotid artery occlusion

BACKGROUND AND PURPOSE: Arterial spin-labeling (ASL) with image acquisition at multiple delay times can be exploited in perfusion MR imaging to visualize and quantify the temporal dynamics of arterial blood inflow. In this study, we investigated the consequences of an internal carotid artery (ICA) occlusion and collateral blood flow on regional timing parameters.MATERIALS AND METHODS: Seventeen functionally independent patients with a symptomatic ICA occlusion (15 men, 2 women; mean age, 57 years) and 29 sex- and age-matched control subjects were investigated. ASL at multiple delay times was used to quantify regional cerebral blood flow (CBF) and the transit and trailing edge times (arterial timing parameters) reflecting, respectively, the beginning and end of the labeled bolus. Intra-arterial digital subtraction angiography and MR angiography were used to grade collaterals.RESULTS: In the hemisphere ipsilateral to the ICA occlusion, the CBF was lower in the anterior frontal (31 ± 4 versus 47 ± 3 mL/min/100 g, P < .01), posterior frontal (39 ± 4 versus 55 ± 2 mL/min/100 g, P < .01), and frontal parietal region (49 ± 3 versus 61 ± 3 mL/min/100 g, P = .04) than that in control subjects. The trailing edge of the frontal-parietal region was longer in the hemisphere ipsilateral to the ICA occlusion compared with that in control subjects (2225 ± 167 versus 1593 ± 35 ms, P < .01). In patients with leptomeningeal collateral flow, the trailing edge was longer in the anterior frontal region (2436 ± 275 versus 1648 ± 201 ms, P = .03) and shorter in the occipital region (1815 ± 128 versus 2388 ± 203 ms, P = .04), compared with patients without leptomeningeal collaterals.CONCLUSION: Regional assessment of timing parameters with ASL may provide valuable information on the cerebral hemodynamic status. In patients with leptomeningeal collaterals, the most impaired territory was found in the frontal lobe.

An obstructive lesion in the internal carotid artery (ICA) causes a reduction of the perfusion pressure in the cerebral circulation. As the cerebral perfusion pressure decreases, pressure is initially maintained by a compensatory vasodilation of the arterioles, followed by an increase in the oxygen extraction fraction.¹ Regionally, the cerebral hemodynamic status depends not only on the degree of carotid obstruction but also on other factors, such as the contribution of collateral pathways.^2,3The collateral circulation can provide alternative routes for oxygenated blood to reach the brain tissue, either through the primary pathways via the circle of Willis or the secondary pathways via leptomeningeal and ophthalmic collaterals.⁴ The combination of a decreased cerebral perfusion pressure and an insufficient primary collateral blood supply may lead to hemodynamic impairment, which eventually can result in a limited clearance of emboli and ischemia.^5,6 Recruitment of the secondary collaterals is associated with further impairment, and its presence may be considered a marker of inadequacy of the primary collateral pathways.^7,8 Because the recruitment of collateral perfusion in patients with an ICA occlusion will lead to longer blood flow routes and a delayed arrival time of the blood, regional knowledge of the arrival times of arterial blood may provide additional information to characterize the collateral flow and may potentially be used to identify hemodynamically impaired regions. The most widely used methods to measure arrival times of blood use dynamic sampling of an injected bolus of contrast agent. However, due to the current concerns regarding contrast use in patients with poor renal function⁹ and ionizing radiation, an alternative without detrimental effects would be of great benefit.Recently, arterial spin-labeling (ASL) was introduced as a noninvasive method capable of assessing cerebral perfusion and the temporal dynamics of arterial blood inflow.¹⁰ The purpose of our study was, first, to investigate hemodynamic parameters in different areas of the brain in patients with an occlusion of the ICA and, second, to evaluate the effect of collateral flow on regional hemodynamics. We used an ASL MR imaging technique with image acquisition at multiple delay times to quantify regionally cerebral blood flow (CBF) and arterial timing parameters (transit and trailing edge times).     

Sixty-four-section CT cerebral perfusion evaluation in patients with carotid artery stenosis before and after stenting with a cerebral protection device

BACKGROUND AND PURPOSE: Brain tissue viability depends on cerebral blood flow (CBF) that has to be kept within a narrow range to avoid the risk of developing ischemia. The aim of the study was to evaluate by 64-section CT (VCT) the cerebral perfusion modifications in patients with severe carotid stenosis before and after undergoing carotid artery stent placement (CAS) with a cerebral protection system.MATERIALS AND METHODS: Fifteen patients with unilateral internal carotid stenosis (≥70%) underwent brain perfusional VCT (PVCT) 5 days before and 1 week after the stent-placement procedure. CBF and mean transit time (MTT) values were measured.RESULTS: Decreased CBF and increased MTT values were observed in the cerebral areas supplied by the stenotic artery as compared with the areas supplied by the contralateral patent artery (P < .001). A significant normalization of the perfusion parameters was observed after the stent-placement procedure (mean pretreatment MTT value, 5.3 ± 0.2; mean posttreatment MTT value, 4.3 ± 0.18, P < .001; mean pretreatment CBF value, 41.2 mL/s ± 2.1; mean posttreatment CBF value, 47.9 mL/s ± 2.9, P < .001).CONCLUSIONS: PVCT is a useful technique for the assessment of the hemodynamic modifications in patients with severe carotid stenosis. The quantitative evaluation of cerebral perfusion makes it a reliable tool for the follow-up of patients who undergo CAS.

Carotid artery stenosis, with its thromboembolic complications causing cerebral ischemia,^1,2 can be successfully treated by carotid endarterectomy (CEA), which significantly reduces the risk of stroke in both symptomatic and asymptomatic patients, as compared with medical therapy alone.^3,4 Alternatively, carotid artery stent placement (CAS) is increasingly used thanks to the development of safe and effective protection systems that help reduce the periprocedural neurologic complications.^5,6 Two recent registry studies (ARCHeR, Caress) have demonstrated that CEA and CAS are comparable in terms of periprocedural complications in symptomatic or asymptomatic patients not presenting comorbidities.^7,8 The overlapping percentage of complications between these 2 techniques at 30 days is 2%.Cerebral perfusion changes, such as an asymmetry in the hemisphere corresponding to the affected carotid artery, have been observed in patients with unilateral severe carotid stenosis, however without a direct correlation to the degree of stenosis.^9,10 A measure of perfusion disturbance as provided by cerebral blood flow (CBF) and mean transit time (MTT) appears to be helpful in evaluating brain with a risk of developing a stroke and eventually in guiding the therapeutic decisions especially in acute ischemic events.¹¹Positron-emission tomography (PET), single-photon emission CT (SPECT), xenon-enhanced CT (Xe-CT), perfusion CT (PCT), and MR imaging have all been applied in the study of brain hemodynamics. However, the scarce availability of PET and SPECT in most radiology departments or the difficulty in obtaining a quantitative measurement by MR imaging has drawn attention for >20 years toward Xe-CT,¹² whose demonstrated accurate measurement of perfusion¹³ has permitted the differentiation of patients with normal CBF¹⁴ from those with reversible neurologic deficits (CBF, 10–20 mL/100 g per minute) or those with infarction (CBF < 10 mL/100 g per minute).¹³ PCT, validated by comparison with Xe-CT^13,14 and widely available in most radiology departments, can be easily performed at the end of a CT scanning and has, therefore, further simplified the approach to brain perfusion evaluation,^15,16 adding further information about hemodynamic parameters such as MTT and cerebral blood volume. More recently, the perfusion study by 64-section CT (VCT), allowing the assessment of a brain volume ≤4 cm, has offered an improved tool of investigation.The aim of our study was to measure by brain perfusional VCT (PVCT) the hemodynamic parameters in the cerebral hemisphere supplied by the severely stenotic internal carotid artery (ICA), in a group of patients undergoing an endovascular treatment with a protection device. The hypothesis is that CBF and MTT values in the hemisphere on the side of the carotid stenosis will be abnormal before the procedure and will approach the values on the contralateral side after the procedure.     

Clinical Application of 3D Arterial Spin-Labeled Brain Perfusion Imaging for Alzheimer Disease: Comparison with Brain Perfusion SPECT

BACKGROUND AND PURPOSE:Alzheimer disease is the most common neurodegenerative disorder with dementia, and a practical and economic biomarker for diagnosis of Alzheimer disease is needed. Three-dimensional arterial spin-labeling, with its high signal-to-noise ratio, enables measurement of cerebral blood flow precisely without any extrinsic tracers. We evaluated the performance of 3D arterial spin-labeling compared with SPECT, and demonstrated the 3D arterial spin-labeled imaging characteristics in the diagnosis of Alzheimer disease.MATERIALS AND METHODS:This study included 68 patients with clinically suspected Alzheimer disease who underwent both 3D arterial spin-labeling and SPECT imaging. Two readers independently assessed both images. Kendall W coefficients of concordance (K) were computed, and receiver operating characteristic analyses were performed for each reader. The differences between the images in regional perfusion distribution were evaluated by means of statistical parametric mapping, and the incidence of hypoperfusion of the cerebral watershed area, referred to as “borderzone sign” in the 3D arterial spin-labeled images, was determined.RESULTS:Readers showed K = 0.82/0.73 for SPECT/3D arterial spin-labeled imaging, and the respective areas under the receiver operating characteristic curve were 0.82/0.69 for reader 1 and 0.80/0.69 for reader 2. Statistical parametric mapping showed that the perisylvian and medial parieto-occipital perfusion in the arterial spin-labeled images was significantly higher than that in the SPECT images. Borderzone sign was observed on 3D arterial spin-labeling in 70% of patients misdiagnosed with Alzheimer disease.CONCLUSIONS:The diagnostic performance of 3D arterial spin-labeling and SPECT for Alzheimer disease was almost equivalent. Three-dimensional arterial spin-labeled imaging was more influenced by hemodynamic factors than was SPECT imaging.

Alzheimer disease (AD) is the most common neurodegenerative disorder with dementia and is becoming a social problem in most developed countries. A practical and economic biomarker for diagnosis of AD is needed. CBF is commonly accepted as a physiologic correlate of brain function.¹ AD is associated with regional decreases in CBF, so the ability of CBF to differentiate between individuals affected by AD and healthy individuals has been evaluated with the use of SPECT.²Arterial spin-labeling (ASL) enables measurement of CBF without any extrinsic tracers by use of magnetically labeled arterial blood water as a diffusible tracer. ASL MR imaging has 2 major modalities: pulsed ASL³ and continuous ASL.⁴ The continuous ASL technique uses continuous adiabatic inversion, whereas pulsed ASL uses a single inversion pulse. The recently developed pulsed-continuous ASL imaging protocol based on 3D stack-of-spirals readouts⁵ is an intermediate method between the conventional pulsed ASL and continuous ASL methods, in that pulsed-continuous offers a longer tag bolus than does pulsed ASL and a higher labeling efficiency than does the amplitude-modulated continuous ASL.^6,7 Each section acquired with 2D ASL experiences a slightly different inflow time; thus, it is difficult to estimate a precise transit time when multiple sections are acquired. The use of 3D acquisition techniques overcomes many of these limitations, allowing both whole-brain coverage and simultaneous acquisition to ensure a unified mean transit time. The SNR of 3D acquisitions can be greater than that of 2D multisection methods. Although ASL has inherently low SNR, mainly because of the relatively small amount of labeled spins in the tissue, pulsed-continuous can provide a better balance between labeling efficiency and SNR than conventional ASL methods. This can improve the accuracy of quantified CBF estimates. Many AD studies by use of ASL have been reported, which indicates that ASL MR imaging is an indispensable technique for studying AD.^8–12 CBF measured with ASL MR imaging can detect regional hypoperfusion in the AD precuneus and bilateral parietal cortex and discriminate individuals with AD from normal subjects. Recent research with the use of pulsed-continuous reported that 3D ASL can evaluate the severity of cognitive impairment as measured by the correlation of CBF with cognition.¹³SPECT is now commonly used for CBF assessment in the diagnosis of AD, so we considered that it was important to evaluate the differences in CBF distribution in perfusion images obtained with both SPECT and ASL by use of similarly behaved diffusible tracers and to demonstrate the characteristics of ASL in comparison with SPECT. To the best of our knowledge, the evaluation of brain perfusion imaging by use of both ASL and SPECT in the same subjects with clinically suspected AD to discriminate the AD group from the non-AD group has not been reported. We used whole-brain 3D ASL MR imaging with pulsed-continuous labeling for CBF measurement in the diagnosis of AD because of its high SNR and the possibilities for improving image quality.In this study, we evaluated the detectability of reduced regional cerebral perfusion in AD by use of 3D ASL compared with brain perfusion SPECT and demonstrated the characteristics of perfusion images obtained by means of 3D ASL.     

Diffuse pachymeningeal hyperintensity and subdural effusion/hematoma detected by fluid-attenuated inversion recovery MR imaging in patients with spontaneous intracranial hypotension

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) MR imaging has advantages to detect meningeal lesions. FLAIR MR imaging was used to detect pachymeningeal thickening and thin bilateral subdural effusion/hematomas in patients with spontaneous intracranial hypotension (SIH).MATERIALS AND METHODS: Eight patients were treated under clinical diagnoses of SIH. Chronologic MR imaging studies, including the FLAIR sequence, were retrospectively reviewed.RESULTS: Initial MR imaging showed diffuse pachymeningeal thickening as isointense in 6 cases, hypoisointense in 1 case, and isohyperintense in 1 case on the T1-weighted MR images, and hyperintense in all cases on both T2-weighted and FLAIR MR images. Dural (pachymeningeal) hyperintensity on FLAIR MR imaging had the highest contrast to CSF, and was observed as linear in all patients, usually located in the supratentorial convexity and also parallel to the falx, the dura of the posterior fossa convexity, and the tentorium, and improved after treatment. These characteristics of diffuse pachymeningeal hyperintensity on FLAIR MR imaging were similar to diffuse pachymeningeal enhancement (DPME) on T1-weighted imaging with gadolinium. Initial FLAIR imaging clearly showed subdural effusion/hematomas in 6 of 8 patients. The thickness of subdural effusion/hematomas sometimes increased transiently after successful treatment and resolution of clinical symptoms.CONCLUSION: Diffuse pachymeningeal hyperintensity on FLAIR MR imaging is a similar sign to DPME for the diagnosis of SIH but does not require injection of contrast medium. FLAIR is useful sequence for the detection of subdural effusion/hematomas in patients with SIH.

Spontaneous intracranial hypotension (SIH) syndrome is characterized by low CSF pressure and positional headache caused by leakage of spinal CSF.^1,2 MR imaging has revolutionized the identification, diagnosis, management, and understanding of SIH. The characteristic MR signs of SIH include diffuse pachymeningeal (dura mater) enhancement (DPME), bilateral subdural effusion/hematomas, downward displacement of the brain, enlargement of the pituitary gland, prominence of the spinal epidural venous plexus, engorgement of cerebral venous sinuses (“venous distension sign,” etc),³ venous sinus thrombosis,⁴ and isolated cortical vein thrombosis.⁵ DPME after gadolinium administration may be the most common and indicative sign^1,2 and forms the basis of the proposed “syndrome of orthostatic headache and diffuse pachymeningeal gadolinium enhancement.”⁶The cause of DPME remains unclear. Histologic examination of meningeal biopsy specimens consistently demonstrates a thin layer of fibroblasts as well as small, thin-walled, dilated blood vessels without evidence of inflammation on the subdural surface, the so-called dural border cell layer.⁷ These findings strongly suggest that dural venous dilation following the Monro-Kellie rule is the most likely explanation of DPME associated with SIH, which states that decreased CSF volume caused by CSF leakage requires volume compensation resulting in meningeal venous hyperemia and subsequent pachymeningeal enhancement.⁸ However, previous studies did not include detailed neuroradiologic evaluations of the pachymeninges in patients with SIH without artificial contrast materials to evaluate the transient and functional changes of the dura mater.⁹Bilateral subdural effusion/hematomas are also classic intracranial signs in the diagnosis of SIH, which again may be explained by the Monro-Kellie rule.^1,6,8 The incidence of subdural effusion/hematomas associated with SIH is 10% to 50% with use of conventional neuroradiologic techniques.^10,11 Subdural effusion/hematomas associated with SIH tend to be thin (typically 2–7 mm), do not cause appreciable mass effect, occur typically over the convexities of the brain, and appear as variable MR signal intensities depending on the fluid protein concentration or presence of blood.¹The fluid-attenuated inversion recovery (FLAIR) pulse sequence cancels the signal intensity from CSF and causes heavy T2 weighting because of the very long TE, resulting in excellent definition of anatomic detail, such as brain surface sulci, and high lesion contrast in areas close to the CSF.¹² This method is commonly used to detect meningeal lesions such as subarachnoid hemorrhage and meningitis.^13–15 Therefore, FLAIR MR imaging may be the optimum sequence to evaluate the thickened dura associated with SIH and to detect the very thin subdural effusion/hematomas located close to the subarachnoid CSF space.Our study used FLAIR MR imaging to examine the thickened dura and subdural effusion/hematomas in patients with SIH.     

Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) may be a useful index of microstructural changes implicated in diffuse axonal injury (DAI) linked to persistent postconcussive symptoms, especially in mild traumatic brain injury (TBI), for which conventional MR imaging techniques may lack sensitivity. We hypothesized that for mild TBI, DTI measures of DAI would correlate with impairments in reaction time, whereas the number of focal lesions on conventional 3T MR imaging would not.MATERIALS AND METHODS: Thirty-four adult patients with mild TBI with persistent symptoms were assessed for DAI by quantifying traumatic microhemorrhages detected on a conventional set of T2*-weighted gradient-echo images and by DTI measures of fractional anisotropy (FA) within a set of a priori regions of interest. FA values 2.5 SDs below the region average, based on a group of 26 healthy control adults, were coded as exhibiting DAI.RESULTS: DTI measures revealed several predominant regions of damage including the anterior corona radiata (41% of the patients), uncinate fasciculus (29%), genu of the corpus callosum (21%), inferior longitudinal fasciculus (21%), and cingulum bundle (18%). The number of damaged white matter structures as quantified by DTI was significantly correlated with mean reaction time on a simple cognitive task (r = 0.49, P = .012). In contradistinction, the number of traumatic microhemorrhages was uncorrelated with reaction time (r = −0.08, P = .71).CONCLUSION: Microstructural white matter lesions detected by DTI correlate with persistent cognitive deficits in mild TBI, even in populations in which conventional measures do not. DTI measures may thus contribute additional diagnostic information related to DAI.

Traumatic brain injury (TBI) is the leading cause of death and disability in young people, with 1.4 million annually reported cases in the United States and an estimated 57 million people worldwide hospitalized with 1 or more TBIs.¹ Furthermore, approximately 80% of the hospital-reported patients with TBI are categorized as having mild TBI on the basis of a Glasgow Coma Scale score between 13 and 15. Although those patients with mild TBI with normal CT findings and no post-traumatic amnesia usually have complete resolution of post-traumatic symptoms within 1 month, approximately 30% of patients with mild TBI with posttraumatic amnesia have persistent posttraumatic symptoms, and a significant number at 1-year postinjury have decreased functional outcome.^2,3Structural imaging studies of acute TBI demonstrate that MR imaging is more sensitive than CT in the number of traumatic lesions visualized.⁴ However, the relationship between focal structural lesions detected by conventional MR imaging and long-term patient outcome is controversial.^3,5-7 Nevertheless, patients with TBI with posttraumatic symptoms often have cognitive impairment, and their cognitive function is a major predictor of poor outcome.^8-12 In particular, attention, working memory, cognitive manipulation of temporal information, and processing speed are vulnerable.^13,14 Sequelae of TBI cause significant disability, which compelled the National Institutes of Health (NIH) to declare mild TBI as a major public health problem.¹⁵Although conventional MR imaging techniques can readily visualize posttraumatic focal structural lesions, they fail to adequately detect diffuse axonal injury (DAI), the key mechanism of damage following TBI.¹⁶ DAI results from unequal rotational or acceleration/deceleration forces that cause multifocal lesions in white matter due to a shear-strain deformation.^17-19 DAI is primarily responsible for transient deficits in cognitive performance in domains such as processing speed, working memory, and attention.^20,21 More recent studies suggest that DAI causes persistent postconcussive symptoms in executive function and memory dysfunction.^8,22-25MR diffusion tensor imaging (DTI) may be used to better assess DAI. In DTI, the characteristics of water diffusion in the brain are used to assess microstructural integrity of white matter pathways.²⁶ In white matter, water diffuses more readily along the orientation of axonal fibers than across the fibers due to hindrance from structural elements such as the axolemma and the myelin sheath. One can calculate the apparent diffusion coefficient (ADC), which is a rotationally invariant measure of the magnitude of diffusion. The degree of directionality of diffusion is termed “anisotropy.” This is the variation in the eigenvalues of the diffusion tensor.²⁷ Fractional anisotropy (FA), a normalized measure of anisotropy, has been shown to be sensitive to microstructural changes in white matter integrity.^28,29 Such measurements quantify the extent of damage following TBI^24,30-32 and are more sensitive than conventional MR imaging to axonal injury in a mouse model of TBI.³³In a group of patients with mild TBI with persistent postconcussive symptoms, we tested the hypothesis that the extent of microstructural white matter injury on DTI would account for deficits in cognitive reaction time, whereas the number of focal lesions on conventional MR imaging would not. The purpose of this study was to determine the predominant areas of damage in mild TBI and whether the spatial extent of white matter injury on DTI can be used as an effective biomarker for global cognitive outcome.     

White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study

BACKGROUND AND PURPOSE: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects.MATERIALS AND METHODS: In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions.RESULTS: Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy.CONCLUSION: Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.

The corpus callosum (CC) is the most important commissural tract in the brain containing myelinated axons transversing the subcortical white matter. The CC serves to unite the 2 hemispheres anatomically and functionally, and CC atrophy may be associated with cognitive and motor deficits.^1–5 A gradual decline in the area and width of the CC has been reported after the fourth decade of life.⁶There is a considerable interindividual variability in the area and shape of the CC in the healthy elderly. Both positive and negative results have been obtained regarding the correlation of CC cross-sectional areas to factors such as sex and handedness,^7–15 number of lacunes and the presence of infarcts in the cerebral hemispheres,^16,17 and/or brain size.¹⁸The mechanism for CC atrophy is poorly understood, but CC atrophy may reflect pathologic changes in subcortical white matter, as reported in patients with multiple sclerosis¹⁹ and vascular dementia.²⁰ In healthy elderly subjects, CC atrophy may result from axonal disruption due to white matter damage.The association between age-related white matter changes (ARWMC) and CC atrophy was previously examined in 5 studies of the elderly with leukoaraiosis,²¹ infarcts and cardiovascular risk factors,¹⁶ Alzheimer disease (AD),^21–23 and healthy elderly controls.^16,21–23 Each of these studies was based on relatively small sample sizes, and taken together, they have not provided a common conclusion concerning the potential influence of ARWMC on the size of the CC. For example, in 3 studies analyzing MR imaging from patients with AD, 1 study (N = 15) found significant correlation between ARWMC and CC atrophy, whereas 2 studies (N = 21 and N = 29) did not find any significant correlation.^22,23 In healthy elderly controls, 3 ^21,22 of 4 studies (n ≤ 29)^16,21–23 found a significant correlation between ARWMC and CC atrophy. The same association was found in a population with cardiovascular risk factors (n = 14) and infarcts (n = 30).¹⁶ However, in the population of elderly subjects with leukoaraiosis (N = 62), Yamauchi et al (2000)²⁴ did not find any significant correlation between ARWMC and CC atrophy.The contradictory conclusions could be due to the use of different methods for segmentation and subdivision of the CC or to different rating techniques for assessment of ARWMC and CC. Small populations and the use of subjective rating scales may obscure potential correlations.The aim of this study was to investigate the correlation between regional ARWMC and atrophy of CC subregions in a large population of nondisabled elderly subjects with leukoaraiosis.     

Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers

BACKGROUND AND PURPOSE:The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method.MATERIALS AND METHODS:Ninety-two healthy volunteers were included: 49 young (age range, 20–30 years) and 43 elderly (age range, 65–80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF_ASL value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF_PCMRI value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g.RESULTS:pCBF_ASL correlated to pCBF_PCMRI (r = 0.73; P < .001). Significant differences were observed between the pCBF_ASL and pCBF_PCMRI values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean ± 2 standard deviations) were −4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF_PCMRI (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF_ASL (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001).CONCLUSIONS:The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

Using well-established perfusion imaging techniques, such as PET, SPECT, or other techniques such as perfusion CT, cerebral blood flow can be quantified within parenchymal tissue and expressed in milliliters per minute per 100 g of brain tissue (mL/min/100 g). These methods require injection of a contrast agent or a radioactive tracer. However, radiotracers are associated with exposure to ionizing radiation, CT contrast agents are nephrotoxic, and perfusion studies of this kind cannot be repeated until the contrast medium or tracer disappears. Using arterial spin-labeling (ASL) MR imaging,¹ it is possible to assess parenchymal CBF (pCBF) noninvasively. Recent developments have enabled quantitative assessment of whole-brain perfusion with ASL within a few minutes.^2,3 The accuracy of pCBF estimates obtained by using ASL, however, is still a subject of discussion.⁴ Age- and sex-related differences in pCBF have been found by using ASL, PET, and SPECT.^5–10 However, these effects are still not fully understood, and no consensus has been established from previously published data.^11,12Total CBF is defined by the 4 arteries that supply the brain (ie, the internal carotid arteries and the vertebral arteries [VAs]). The blood flow of these arteries, and thus the total CBF, can be measured with good accuracy at the level of the foramen magnum by using 2D phase-contrast MR imaging (PCMRI).^13,14 Using high-resolution morphologic MR imaging data and postprocessing software, the total volume of the brain parenchymal tissue can be assessed. Total CBF can be obtained accurately with PCMRI (shown here as pCBF_PCMRI values),¹⁴ and brain parenchymal volume can be measured accurately¹⁵ from the T1 sequence. By dividing flow by volume, pCBF_PCMRI can be estimated with expected good accuracy and used as a reference to evaluate the accuracy of pCBF obtained via ASL (pCBF_ASL).The aim of this study was to investigate the accuracy of a clinically implemented pseudocontinuous ASL method for assessing pCBF in 92 healthy individuals by using PCMRI as the reference method. The effects of aging and sex on pCBF were assessed by using both methods, and the results were compared.     

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

BACKGROUND AND PURPOSE:White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit.MATERIALS AND METHODS:In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression.RESULTS:Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized β = −0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized β = −0.065, P = .643) or GM CBF (standardized β = −0.035, P = .382) in linear regression.CONCLUSIONS:Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.

White matter hyperintensities (WMHs) of presumed vascular origin are a common finding on brain MR imaging in elderly individuals. WMH prevalence estimates in asymptomatic older individuals range from 45% to >90%, depending on age and severity.¹ Clinically, WMHs are associated with cognitive decline, neuropsychiatric symptoms, loss of functional independence, and increased mortality.^2,3 Advanced age and hypertension are the strongest risk factors for WMHs, especially for the confluent subtype.^1–4The pathophysiology of WMHs has not yet been fully elucidated. They often appear together with other signs of cerebral small-vessel disease, an umbrella term for neuroradiologic anomalies often found in asymptomatic elderly individuals.^4,5 Histologically, confluent WMHs appear as a continuum of increasing tissue damage resembling chronic low-grade ischemia.^1,5 Therefore, WMHs may be the result of chronic low-grade white matter hypoperfusion.^1,5,6 In agreement, CBF within WMHs is lower compared with normal-appearing WM (NAWM).^7–14Whether WMHs are associated with a lower cerebral perfusion in general, also involving the surrounding NAWM and gray matter, is unclear. Some findings suggest that WMHs may relate to lower whole-brain or GM perfusion,^7,11,15,16 and WMHs have been associated with reduced blood flow velocity in the large intracranial arteries, outside the WM.^17–19 On a broader level, the association between WMHs and chronic cardiac disease also hints at a relation with general perfusion.²⁰ WMHs primarily originate in physiologically poorly perfused areas (ie, the periventricular and deep WM), explaining how even a slight cerebral perfusion deficit could provoke low-grade ischemia in those regions associated with WMHs.^21,22 Low perfusion in NAWM has also been associated with subsequent WMH development.²³ While these findings seem to suggest that WMHs are related to a perfusion deficit extending beyond the WMHs, current evidence remains circumstantial.In this study, we address the hypothesis that WMHs are associated with lower cerebral perfusion, not only within the WMHs but also in the surrounding NAWM and GM. If so, this could be a first step in determining why WMHs form in elderly individuals and toward preventive treatment. Because age and hypertension are the strongest risk factors for asymptomatic WMHs, we tested this hypothesis in a large cohort of community-dwelling elderly with hypertension, by using noninvasive arterial spin-labeling MR imaging. Arterial spin-labeling was chosen because this method of perfusion measurement allows noninvasive (ie, without contrast) MR imaging measurement of CBF within a scanning time of as little as 4 minutes, facilitating large-scale CBF measurement in research settings and eventually enabling clinical application.     

Comparison of three different methods for measurement of cervical cord atrophy in multiple sclerosis

BACKGROUND AND PURPOSE: Evidence is mounting that spinal cord atrophy significantly correlates with disability in patients with multiple sclerosis (MS). The purpose of this work was to validate 3 different measures for the measurement of cervical cord atrophy on high-resolution MR imaging in patients with MS and in normal control subjects (NCs). We also wanted to evaluate the relationship between cervical cord atrophy and clinical disability in the presence of other conventional and nonconventional brain MR imaging metrics by using a unique additive variance regression model.MATERIALS AND METHODS: We studied 66 MS patients (age, 41.2 ± 12.4 years; disease duration, 11.8 ± 10.7 years; Expanded Disability Status Scale, 3.1 ± 2.1) and 19 NCs (age, 30.4 ± 12.0 years). Disease course was relapsing-remitting (34), secondary-progressive (14), primary-progressive (7), and clinically isolated syndrome (11). The cervical cord absolute volume (CCAV) in cubic millimeters and 2 normalized cervical cord measures were calculated as follows: cervical cord fraction (CCF) = CCAV/thecal sac absolute volume, and cervical cord to intracranial volume (ICV) fraction (CCAV/ICV). Cervical and brain lesion volume measures, brain parenchyma fraction (BPF), and mean diffusivity were also calculated.RESULTS: CCAV (P < .0001) and CCF (P = .007) showed the largest differences between NCs and MS patients and between different disease subtypes. In regression analysis predicting disability, CCAV was retained first (R² = 0.498; P < .0001) followed by BPF (R² = 0.08; P = .08). Only 8% of the variance in disability was explained by brain MR imaging measures when coadjusted for the amount of cervical cord atrophy.CONCLUSIONS: 3D CCAV measurement showed the largest differences between NCs and MS patients and between different disease subtypes. Cervical cord atrophy measurement provides valuable additional information related to disability that is not obtainable from brain MR imaging metrics.

MR imaging of the brain is a sensitive tool for making a diagnosis of multiple sclerosis (MS). Abnormalities of brain MR imaging are present in more than 95% of patients with clinically definite MS; however, there is poor correlation between disability and the number and volume of focal brain lesions visible on MR imaging.¹Involvement of the spinal cord, especially of the cervical cord,^2,3 is of particular significance in the development of physical disability in patients with MS.^4,5 During the course of their disease, approximately 80% of patients with MS present with spinal cord symptoms.⁶ Conventional T2-weighted spinal cord imaging is sensitive in detecting spinal cord lesions and their changes over time.^7,8 However, measures of cord T2 lesion number and volume failed to show a significant relationship with disability and have poor prognostic value for disability accumulation over the mid-to-long term.^2,3 Evidence is mounting that spinal cord atrophy significantly correlates with disability.^5,9–11Atrophy of the spinal cord in MS is thought to reflect inflammatory tissue injury, demyelination, and axonal loss. Postmortem pathologic studies have documented spinal cord axonal loss in MS.^12,13 However, whereas the correlation between central nervous system atrophy and disability has been interpreted as a reflection of axonal loss in pre-existing lesions,^14–16 axonal loss does not appear to directly affect the cross-sectional cord area in pathologic studies.² Measurement of spinal cord atrophy has demonstrated value in the clinical realm. Serial MR imaging of the spinal cord has shown evidence of disease activity undetectable on clinical examination, thereby increasing the diagnostic sensitivity of MR imaging for patients with suspected MS.¹⁷ Spinal cord abnormalities on MR imaging are not restricted only to patients presenting with spinal cord symptoms, because changes suggestive of atrophy may be seen before any manifestation of clinical symptoms. It has been shown that atrophy of the cervical spinal cord is a useful measure for determining clinical disability^10,15,18 and monitoring disease progression,¹⁹ as well as therapeutic drug effects in MS.²⁰Key problems in the evaluation of spinal cord atrophy have been related to poor resolution of MR imaging, small size of the cord, and surrounding fat, bone, and CSF that can cause artifacts and, as a consequence, compromise the final image quality. Indeed, artifacts related to pulsation and respiratory cardiac motion have also been considered.^2,3 This led in most of the earlier studies to unacceptable error in manual delineation of the cord/CSF interface.² The technical challenges of spinal cord imaging posed by the size and anatomy of the cord and by its surrounding structures have been addressed in recent years by improved receiver coils, fast imaging, 3D imaging, motion suppression, and cardiac gating. Subsequently, interest has emerged in a reproducible semiautomated measurement of the cord cross-sectional area²¹ and its improved measurement by reduction of partial volume effect,²² as well as by 3D extraction of the cord surface area.²³The goal of the present study was to investigate whether spinal cord atrophy in MS may be assessed by measurement of the whole cervical cord volume rather than by the traditional cross-sectional area approach at level C2/C3. To improve the accuracy and precision of cervical cord volume measurements, a semiautomated edge detection technique was used to create a tissue-boundary map from 3D volumetric scans of the cervical cord. Therefore, the objectives of the present cross-sectional study were first to validate this original method for measuring whole cervical cord volume by comparing 19 normal control subjects (NCs) and 65 patients with MS with different disease subtypes. We also evaluated the relationship between absolute and normalized cervical cord atrophy and clinical disability in the presence of other conventional and nonconventional brain MR imaging metrics using a unique additive variance regression model.     

Sinonasal organized hematoma: CT and MR imaging findings

BACKGROUND AND PURPOSE: Sinonasal organized hematoma (OH) is an uncommon, nonneoplastic benign condition that can be locally aggressive. The purpose of this work was to characterize the CT and MR imaging findings of sinonasal OH.MATERIALS AND METHODS: CT (n = 11) and MR (n = 10) images of 12 patients (9 men and 3 women; mean age, 41 years; range, 12–76 years) with pathologically proved sinonasal OH were retrospectively reviewed. Particular attention was put on the location, shape, size, extent, internal architecture, and enhancement pattern of the lesion and associated sinus wall change.RESULTS: The lesions were seen as an expansile (n = 9) or nonexpansile (n = 3) mass, ranging in size from 2.2 to 6.0 cm (mean, 4.2 cm), primarily involving the maxillary sinus (n = 11) or nasal cavity (n = 1) unilaterally. The ipsilateral nasal cavity was also involved in 9 of 11 maxillary sinus lesions. Smooth sinus wall erosion other than the medial maxillary sinus wall was noted in 8 lesions. The internal architecture was best displayed on T2-weighted MR images on which all of the lesions were seen as a mixture of marked heterogeneous hypointensity and isointensity, surrounded by a hypointense peripheral rim, reflecting histologic heterogeneity of the lesion composed of hemorrhage, fibrosis, and neovascularization. Marked irregular nodular, papillary, or frondlike enhancement at the areas of neovascularization was also a typical finding seen in all of the lesions.CONCLUSION: An expansile soft tissue mass, smooth sinus wall erosion, marked heterogeneous signal intensity with a hypointense peripheral rim on T2-weighted MR images, and marked irregular nodular, papillary, or frondlike enhancement are characteristic CT and MR imaging findings of sinonasal OH.

Sinonasal organized hematoma (OH) is an uncommon, nonneoplastic benign condition that can be locally aggressive. Without careful evaluation of all of the imaging features, this may be mistaken for a malignant lesion both clinically and radiologically. It most commonly affects the maxillary sinus and can result from various causes of hemorrhage with chronic hematoma formation, followed by the process of organization through fibrosis and neovascularization.^1,2 Since the first report by Ozhan et al³ in a patient with von Willebrand disease, only fewer than 40 cases have been reported in the English literature under various names, including pseudotumor,^3,4 hematoma,⁵ organized or organizing hematoma,^1,2,6–8 and hematoma-like mass of the maxillary sinus.⁹Correct preoperative diagnosis of sinonasal OH is important to avoid unnecessary extensive surgery, because this condition is curative with a simple, conservative surgical approach and rarely recurs. Although there have been a few reports on the CT findings of sinonasal OH,^1–3,5–9 which are reported to be rather nonspecific, to our knowledge, the MR imaging features have not systematically been analyzed previously. Only 2 studies had briefly mentioned the MR imaging features.^8,9 Yagisawa et al⁹ reported that masses were well demarcated from the surrounding structures and heterogeneous in signal intensity on both T1- and T2-weighted MR images. Song et al⁸ reported that the lesions appeared as isosignal intensity with a margin that had a slightly higher signal intensity on T1-weighted images and a mosaic of various signal intensities and a low signal intensity rim on T2-weighted images. The purpose of this study was to report the CT and MR imaging findings, which are believed to be characteristic for sinonasal OH.     

A T1 hyperintense perilesional signal aids in the differentiation of a cavernous angioma from other hemorrhagic masses

BACKGROUND AND PURPOSE: A cavernous angioma is a developmental vascular malformation with a high risk of hemorrhage. The purpose of this work was to retrospectively determine whether an MR sign of T1 hyperintense perilesional signal intensity is useful for the differentiation of cavernous angioma from other hemorrhagic cerebral masses.MATERIALS AND METHODS: The institutional review board approved this study. We retrospectively evaluated the MR images of 72 patients with acute or subacute cerebral hemorrhagic lesions with perilesional edema (29 cavernous angiomas, 13 glioblastomas, 1 oligodendroglioma, 16 metastatic tumors, and 13 intracerebral hemorrhages) for the presence of T1 hyperintense perilesional signal intensity. In addition, T1 signal intensities of a perilesional edema were quantitatively analyzed. In cavernous angiomas, volumes of hemorrhagic lesions and perilesional edemas, lesion locations, presence of contrast enhancement, and time intervals between symptom onset and MR imaging were also assessed. Data were analyzed using unpaired t test or Fisher exact test.RESULTS: T1 hyperintense perilesional signal intensity sign was found in 18 (62.1%) of 29 cavernous angiomas, in 1 (6.3%) of 16 metastases, and in 0 primary brain tumors or intracerebral hemorrhages. Sensitivity, specificity, and positive predictive value of this sign for cavernous angioma were 62%, 98%, and 95%, respectively. The perilesional T1 hyperintensity was significantly higher in cavernous angiomas (P = .045) than in normal white matter. Perilesional edema volumes were larger in cavernous angiomas with the MR sign than in cavernous angiomas without the sign (P = .009).CONCLUSION: When the MR sign of T1 hyperintense perilesional signal intensity is present, there is a high probability of cavernous angioma being present in the brain, and this MR sign may be helpful for differentiating cavernous angioma from hemorrhagic tumors and intracerebral hemorrhages.

A cavernous angioma, also known as a cavernous malformation or cavernoma, is a developmental vascular malformation that is typically a discrete multilobulated, berrylike lesion containing hemorrhage in various stages of evolution. Hemorrhage is a common complication of a cavernous angioma and is the cause of the first presentation in 30% of cases.^1,2 The reported annual risk of hemorrhage in a cavernous angioma varies widely (1%–6.8%).^3–5MR imaging is the most important diagnostic technique for the detection of cavernous angiomas and frequently produces highly characteristic images. Typically, cavernous angiomas show a mixed signal intensity core, a reticulated “popcorn ball” appearance, and a “T2 blooming sign,” which is due to a low signal intensity hemosiderin rim that completely surrounds the lesion.^6,7 Susceptibility-weighted imaging, such as a T2* gradient-echo image, is more useful for the detection of the hemosiderin deposit and the diagnosis of a cavernous angioma. The typical MR signs of “popcorn ball” appearance and “T2 blooming sign” on T2-weighted images have been reported to be found in approximately 50%–67% of cavernous angiomas.^2,8Based on these MR findings, although diagnosis is usually straightforward in typical cases of a cavernous angioma, lesions with unusual MR features may be misdiagnosed as primary or metastatic brain tumors.^9–18 The atypical MR features of cavernous angiomas include variable or strong enhancement,^2,9,10,19 a large perilesional vasogenic edema and mass effect,^2,10,19,20 the cystic form of a cavernous angioma,^9,20,21 and the manifestations of a recent hematoma.^22,23 Cavernous angiomas that present with recent hemorrhage and with a surrounding edema may mimic a primary or secondary brain tumor with hemorrhage; these lesions may be frequently underestimated as a sole hematoma.Recently, we encountered some cases that showed T1 hyperintensity in a perilesional edema around the acute or subacute hemorrhagic masses. As far as we know, the MR feature of T1 hyperintensity in a perilesional edema around a hemorrhagic mass has not yet been documented. The aim of this study was to determine in a retrospective study whether the MR sign of a T1 hyperintense perilesional signal intensity is useful for differentiating a cavernous angioma from other hemorrhagic cerebral masses.     

Combined 3T diffusion tensor tractography and 1H-MR spectroscopy in motor neuron disease

BACKGROUND AND PURPOSE: Diagnostic confidence in motor neuron disease may be improved by the use of advanced MR imaging techniques. Our aim was to assess the accuracy (sensitivity/specificity) and agreement of combined ¹H-MR spectroscopy (proton MR spectroscopy) and diffusion tensor imaging (DTI) at 3T in patients with suspected motor neuron disease regarding detection of upper motor neuron (UMN) dysfunction.MATERIALS AND METHODS: Eighteen patients with suspected motor neuron disease were studied with MR spectroscopy/DTI and clinically rated according to the El-Escorial and ALSFRS-R scales. For MR spectroscopy, absolute N-acetylaspartate (NAA), choline (Cho), and phosphocreatine (PCr) concentrations and relative NAA/Cho and NAA/PCr ratios of corresponding volumes of interest within the primary motor cortex were calculated. For DTI, fractional anisotropy (FA) and mean diffusivity (MD) were measured bilaterally at the level of the precentral gyrus, corona radiata, internal capsule, cerebral peduncles, pons, and pyramid. FA and MD statistics were averaged on the corticospinal tracts (CSTs) as a whole to account for a region-independent analysis.RESULTS: MR spectroscopy indicated NAA reduction beyond the double SD of controls in 6 of 8 patients with clinical evidence for UMN involvement. Congruently, the mean FA of these patients was significantly lower in the upper 3 regions of measurements (P < .01). Overall, MR spectroscopy and DTI were concordant in all except 3 cases: 1 was correctly excluded from motor neuron disease by DTI (genetically proved Kennedy syndrome), whereas MR spectroscopy indicated CST involvement. MR spectroscopy and DTI each were false-positive for CST affection in 1 patient with lower motor neuron involvement only.CONCLUSION: Combined MR spectroscopy/DTI at 3T effectively adds to the detection of motor neuron disease with a high degree of accordance.

Amyotrophic lateral sclerosis (ALS), Lou Gehrig syndrome or Charcot disease, is the most common progressive motor neuron disease.¹ Classic ALS affects the upper (UMN) and lower motor neurons (LMN), but cases with predominant UMN or LMN involvement also occur. It is still debated whether primary lateral sclerosis (PLS) and ALS are distinct disorders or manifestations of a single disorder, and a classification into ALS, UMN–dominant ALS, and PLS has been proposed to systematize future trials,² hence the correctness of UMN assessment is crucial.In addition to traditional diagnostic steps, such as electromyography, transcranial magnetic stimulation,^3,4 and assessment according to established clinical rating scales (eg, El-Escorial [EE]⁵ or ALS Functional Rating Scale-Revised [ALSFRS-R⁶]), recent promising attempts to improve diagnostic confidence of UMN assessment used advanced MR imaging techniques: ¹H-MR spectroscopy (proton MR spectroscopy),^7–11 diffusion tensor imaging (DTI),^12–19 diffusion tensor tractography (DTT),²⁰ or combinations thereof.^21,22 However, systematic evaluation of their concordance in the same patients is still rare.^21,23To obtain a definite diagnosis early in the disease is important for therapeutic intervention,^21,24 quality of life,^17,25,26 and monitoring therapeutic trials.^16,22 Cervical myelopathy, Kennedy syndrome (spinobulbar muscle atrophy, [SBMA]), peripheral nerve lesions, and multifocal polyneuropathy are, among others, differential diagnoses that have to be excluded. The clinical diagnosis is especially difficult when UMN involvement remains unclear. The previously mentioned techniques not only hold the promise of a more specific and potentially objective MR imaging measure but may even lead to a biomarker of disease severity.In contrast, most characteristics observed on structural MR imaging, such as corticospinal tract (CST) hyperintensities in T2-weighted, proton density, and fluid-attenuated inversion recovery (FLAIR) imaging^27–32; hypointense precentral gyrus changes^33,34; or marked frontal or callosal atrophy,³⁵ are rather uncertain.^31,32 CST hyperintensities are frequently found in healthy individuals, whereas the hypointense precentral gyrus sign apparently is motor neuron disease–specific according to Ishikawa et al³³ but occurs only in a minority of patients with ALS. To our knowledge, none of these signs have yet been studied at 3T. The principal aim of the present study was to evaluate the diagnostic accuracy of combined MR spectroscopy and DTI at 3T as an additional diagnostic tool in patients with suggested motor neuron disease and to provide an estimate of their concordance when applied to the same patients.     

Nontraumatic skull base defects with spontaneous CSF rhinorrhea and arachnoid herniation: imaging findings and correlation with endoscopic sinus surgery in 27 patients

BACKGROUND AND PURPOSE: Defects at the skull base leading to spontaneous CSF rhinorrhea are rare lesions. The purpose of our study was to correlate CT and MR findings regarding the location and content of CSF leaks in 27 patients with endoscopic sinus surgery observations.MATERIALS AND METHODS: Imaging studies in 27 patients with intermittent CSF rhinorrhea (CT in every patient including 10 examinations with intrathecal contrast, plain CT in 2 patients, and MR in 15 patients) were analyzed and were retrospectively blinded to intraoperative findings.RESULTS: CT depicted a small endoscopy-confirmed osseous defect in 3 different locations: 1) within the ethmoid in 15 instances (53.6% of defects) most commonly at the level of the anterior ethmoid artery (8/15); 2) adjacent to the inferolateral recess of the sphenoid sinus in 7 patients including one patient with bilateral lesions (8/28 defects, 28.6%); 3) within the midline sphenoid sinus in 5 of 28 instances (17.9%). Lateral sphenoid defects (3.5 ± 0.80 mm) were larger than those in ethmoid (2.7 ± 0.77 mm, P ≤ 0.029) or midsphenoid location (2.4 ± 0.65 mm, P ≤ 0.026). With endoscopy proven arachnoid herniation in 24 instances as reference, MR was correct in 14 of 15 instances (93.3%), CT cisternography in 5 of 8 instances (62.5%). Plain CT in 1 patient was negative.CONCLUSION: In patients with a history of spontaneous CSF rhinorrhea, CT was required to detect osseous defects at specific sites of predilection. MR enabled differentiating the contents of herniated tissue and allowed identification of arachnoid tissue as a previously hardly recognized imaging finding.

The term “spontaneous” CSF rhinorrhea has been applied to describe nasal discharge of CSF unrelated to trauma, surgery, malformation, tumor, or previous radiation therapy.^1–4 Spontaneous CSF rhinorrhea is uncommon. Estimates of the spontaneous cause among all causes of CSF rhinorrhea are subject to variation ranging from only 6%,⁵ 11.4%,⁶ 14%,³ 21%,⁷ to 23%.⁸ Periodic release of CSF from the nose was first described by Galen in 200 B.C. and was considered a physiologic phenomenon until Thomson, in 1899, assembled 21 patients in a monograph reporting spontaneous CSF rhinorrhea as a pathologic clinical entity.^9,10Spontaneous CSF rhinorrhea has been recognized as a distinct entity with respect to clinical presentation,^2,11,12 treatment,^13–15 and propensity for recurrence.^8,16,17 As early as 1968, Ommaya et al⁹ postulated the existence of “high-pressure leaks” related to intracranial tumors and of “normal pressure leaks” occasionally associated with empty sella. The role of empty sella as an indicator of raised intracranial pressure as well was supported by the observation of elevated CSF pressure in individual patients¹¹ and in a series of 10 patients who underwent lumbar puncture after sealing of the defect.¹⁸ In addition to the presence of an empty sella as a radiologic sign,¹⁹ a common clinical constellation in patients with spontaneous CSF rhinorrhea is female sex, middle age, and obesity.^{8,14,15,18–22}Spontaneous CSF leaks have been postulated to represent a manifestation of benign intracranial hypertension²² or pseudotumor cerebri.²³ Pulsatile-increased hydrostatic pressure is capable of bone erosion during the course of many years.^2,24 To become effective as a CSF leak, bone erosion and creation of an osteodural defect is required to occur at pneumatized parts of the skull base leading to communication of the subarachnoid space with the sinonasal spaces or temporal bone cavity. Related to CSF rhinorrhea, a review of the literature up to 1972¹⁰ identified the cribriform plate, craniopharyngeal canal, sella, and spheno-occipital synchondrosis as possible sites of predilection. Arachnoid granulations in proximity to the ethmoid and sphenoid sinus have been implicated as precursors of osteodural leaks.² Accordingly, arachnoid granulations causing erosion of the temporal bone may present with CSF otorrhea.^2,25,26Among the imaging techniques used to localize the site of the fistula, radionuclide isotope cisternography and CT cisternography were of limited sensitivity in 66% of patients only.³ When active leaks were present, CT cisternography provided positive results in 85% of patients.²⁷ However, in cases of inactive fistulas, CT cisternography failed to recognize the site of leakage in 27.7%²⁸ and in 19% of patients.²⁹ Advances in CT and MR imaging techniques have improved sensitivity, which amounted to 88.25%³⁰ and 93%³¹ for high-resolution CT and for MR cisternography to 89%,^6,31 93.6%,²⁸ and 100%^32,33 even in patients with inactive leaks. Therefore, high-resolution CT, MR cisternography, or a combination of both techniques have replaced the previously used invasive procedures.A confounding nomenclature exists regarding the contents of osteodural defects such as meningocele,^10,14 meningoencephalocele,⁴ encephalocele,^11,34 meningeal or arachnoid hernia,^24,35 arachnoid diverticulum,³⁶ or arachnoid cyst.³⁷ These differing designations reflect variable contents of herniation and occasional inaccuracy because of the limited ability to visualize the lesions by imaging^24,29 and during transcranial surgery.^1,10 Knowledge of the contents of herniation may modify the grafting technique and therefore facilitates preoperative planning.¹⁶ The endoscopic skull base approach has rendered direct visualization of the defect and its contents feasible.^38–40 Therefore, endoscopy was chosen as a standard of reference in this study. CT and MR findings in this series of patients with spontaneous CSF rhinorrhea were particularly assessed regarding the contents of herniation and location and correlated with endoscopy. Predisposing factors (arachnoid granulation, empty sella) and the size of the osseous defect were assessed on CT images.