Role of apparent diffusion coefficient values in differentiation between malignant and benign solitary thyroid nodules

BACKGROUND AND PURPOSE: Accurate imaging characterization of a solitary thyroid nodule has been clearly problematic. The purpose of this study was to evaluate the role of the apparent diffusion coefficient (ADC) values in the differentiation between malignant and benign solitary thyroid nodules.MATERIALS AND METHODS: A prospective study was conducted in 67 consecutive patients with solitary thyroid nodules who underwent diffusion MR imaging of the thyroid gland. Diffusion-weighted MR images were acquired with b factors of 0, 250, and 500 s/mm² by using single-shot echo-planar imaging. ADC maps were reconstructed. The ADC values of the solitary thyroid nodules were calculated and correlated with the results of histopathologic examination. Statistical analysis was performed.RESULTS: The mean ADC value of malignant solitary thyroid nodules was 0.73 ± 0.19 × 10⁻³ mm²/s and of benign nodules was 1.8 ± 0.27 × 10⁻³ mm²/s. The mean ADC values of malignant nodules were significantly lower than those of benign ones (P = .0001). There were no significant differences between the mean ADC values of various malignant thyroid nodules, but there were significant differences between the subtypes of benign thyroid nodules (P = .0001). An ADC value of 0.98 × 10⁻³ mm²/s was proved as a cutoff value differentiating between benign and malignant nodules, with 97.5%, 91.7%, and 98.9% sensitivity, specificity, and accuracy, respectively.CONCLUSION: The ADC value is a new promising noninvasive imaging approach used for differentiating malignant from benign solitary thyroid nodules.

Nodular thyroid is commonly detected on palpation in 4%–7% of the population,^1,2 on sonographic examination in 10%–40%, and by pathologic examination at autopsy in 50%.^3,4 In contrast, compared with the high prevalence of nodular thyroid disease, thyroid cancer is rare. The challenge of imaging thyroid nodules is to reassure most patients who have benign disease and to diagnose the minority of patients who will prove to have a malignancy.^5,6Ultrasonography has been used in the assessment of the thyroid nodules as a primary imaging technique.^2,7,8 Currently, there is no single sonographic criterion that can reliably distinguish benign from malignant thyroid nodules.^4,9 The results of predicting thyroid cancer with color Doppler sonography are controversial, with some reporting that Doppler sonography is helpful and others reporting that it did not improve diagnostic accuracy.^4,5,10,11 The hazards of radiation exposure are unavoidable in nuclear scintigraphy,² and not all functioning nodules on scintigraphy are benign.^6,9 The risk of cancer in a cold nodule is 4 times more common than in a hot nodule.^3,6 Fine-needle aspiration biopsy (FNAB) with cytologic evaluation is commonly used, but it is inconclusive in 15%–20% of patients, in addition to the possible, but less likely, associated hemorrhage.^2,4 The incidence of cancer in patients with thyroid nodules selected for FNAB is approximately 9.2%–13%.⁵ FNAB is considered an effective method for differentiating between benign and malignant thyroid nodules.^4,7,12–14Routine T1- and T2-weighted MR imaging has a limited role in the evaluation of thyroid nodules. It cannot distinguish benign from malignant nodules or assess the functional status of thyroid nodules.^12–15 Diffusion-weighted MR imaging has been used to characterize head and neck tumors, in which there are significant differences in the apparent diffusion coefficient (ADC) values of malignant tumors and benign lesions.^16–19 Tezuka et al,²⁰ in their study using diffusion-weighted MR imaging to assess the thyroid function, reported that the ADC values of patients with Grave''s disease exceeded those of patients with subacute thyroiditis, with a sensitivity and specificity of 75% and 80%, respectively, in differentiating between both disease entities. They concluded that diffusion-weighted MR imaging could be clinically important in evaluating the thyroid function. To our knowledge, there have been no articles about diffusion-weighted MR imaging evaluating thyroid nodules.The aim of our study was to evaluate the role of ADC values in differentiating between malignant and benign solitary thyroid nodules.     

Differentiation between classic and atypical meningiomas with use of diffusion tensor imaging

BACKGROUND AND PURPOSE:The differentiation between classic and atypical meningiomas may have implications in preoperative planning but may not be possible on the basis of conventional MR imaging. Our hypothesis was that classic and atypical meningiomas have different patterns of intratumoral water diffusion that will allow for differentiation between them.MATERIALS AND METHODS:Preoperative diffusion tensor imaging (DTI) was performed in 12 classic and 12 atypical meningiomas. Signal intensity of solid-enhancing tumor regions on diffusion-weighted trace images and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps was assessed. Regions of interest (ROIs) were placed in solid-enhancing regions, peritumoral edema, and contralateral normal-appearing white matter (NAWM) to measure tensor metrics including major (λ₁), intermediate (λ₂) and minor eigenvalues (λ₃) and FA and ADC values. Distribution of tensor shapes within enhancing tumors was calculated for all tumors. Differences between classic and atypical meningiomas in tumor signal intensity, intratumoral and peritumoral tensor metrics, as well as tensor shapes distribution were statistically analyzed.RESULTS:A significantly greater proportion of atypical meningiomas were isointense and hypointense on ADC maps (P = .007). Classic meningiomas had significantly lower FA (P = .012), higher ADC (P = .011), greater λ₂ (P = .020) and λ₃ (P = .003). There was significantly more spherical diffusion in classic than in atypical meningiomas (P = .020). All diffusion tensor metrics for peritumoral edema of the 2 tumor groups did not differ.CONCLUSION:DTI showed that intratumoral microscopic water motion is less organized in classic than in atypical meningiomas. This feature may allow for noninvasive differentiation between classic and atypical meningiomas.

Meningiomas account for between 16% and 20% of primary intracranial tumors.¹ According to the World Health Organization (WHO) classification system, 78% of meningiomas are grade I, 20.4% are grade II, and 1.6% are grade III.² Grades II and III meningiomas are more aggressive than grade I meningiomas. Five-year recurrence rates are 12% for benign meningiomas and 41% for atypical meningiomas.² Initial extent of tumor resection and histologic grade are key determinants for recurrence.³ Therefore, prospectively identifying their histologic grades can be clinically beneficial in treatment planning. Although conventional MR imaging can provide detailed morphologic information of meningiomas, its value in the prediction of WHO grades is limited.⁴According to the WHO classification,⁵ classic meningiomas differ from atypical ones in their number of mitoses, cellularity, and nucleus-to-cytoplasm ratio (N/C ratio) as well as their histologic patterns. Complex microstructural barriers in brain tissue, such as white matter tracts, cell membranes, and capillary vessels result in a tendency for water molecules to diffuse with direction (anisotropic diffusion) rather than equally in all directions (isotropic diffusion). Isotropic diffusion-weighted imaging (DWI), which measures average magnitude of water motion in apparent diffusion coefficient (ADC), has shown controversial results for differentiating classic from atypical meningiomas.^6-8 In contrast to isotropic DWI, diffusion tensor imaging (DTI) provides information about magnitude and directionality of water diffusion⁹ and thus may be able to measure the differences in intratumoral diffusion anisotropy as a result of histologic differences between classic and atypical meningiomas. On the other hand, peritumoral edema associated with meningiomas, regardless of classic or atypical subtypes, has always been considered a purely vasogenic edema (ie, absence of tumor cell infiltration).^10,11Our first hypothesis was that intratumoral diffusion anisotropy is different between these 2 tumor types and that differences in diffusion anisotropy as detected by DTI allow differentiation between them. Our second hypothesis was that anisotropic diffusion measured in peritumoral edema with DTI will not be different between classic and atypical meningiomas.     

Differentiation of benign and malignant pathology in the head and neck using 3T apparent diffusion coefficient values: early experience

BACKGROUND AND PURPOSE: The purpose of this work was to study differences in apparent diffusion coefficient (ADC) values between benign and malignant head and neck lesions at 3T field strength imaging.MATERIALS AND METHODS: Our study population in this retrospective study was derived from the patient population who had undergone routine neck 3T MR imaging (for clinical indications) from December 2005 to December 2006. There were 33 patients identified: 17 with benign and 16 with malignant pathologies. In all of the subjects, conventional MR imaging sequences were performed apart from diffusion-weighted sequences. The mean ADC values in the benign and malignant groups were compared using an unpaired t test with unequal variance with a P < 0.05 considered statistically significant.RESULTS: There was a statistically significant difference (P = .004) between the mean ADC values (in 10⁻³ mm²/s) in the benign and malignant lesions (1.505 ± 0.487; 95% confidence interval, 1.305–1.706, and 1.071 ± 0.293; 95% confidence interval, 0.864–1.277, respectively). There were 2 malignant lesions with ADC values higher than 1.3 × 10⁻³ mm²/s and 5 benign lesions with ADC values less than 1.3 × 10⁻³ mm²/s. The lack of overlap of ADC values within 95% confidence limits suggests that a 3T ADC value of 1.3 × 10⁻³ mm²/s may be the threshold value for differentiation between benign and malignant head and neck lesions.CONCLUSION: ADC values of benign and malignant neck pathologies are significantly different at 3T imaging, though larger studies are required to establish threshold ADC values that can applied in daily clinical practice.

CT and conventional MR imaging (using spin-echo [SE] T1-weighted and T2-weighted images) are extensively used at present for evaluation of both palpable and nonpalpable neck lesions, as well as characterization of biologic behavior using imaging criteria, which include necrosis, invasion of adjacent structure, and perineural spread. However, it is not uncommon to encounter lesions that have indeterminate findings on cross-sectional imaging and necessitate further investigation.Diffusion-weighted imaging (DWI) with calculation of apparent diffusion coefficient (ADC) values has been investigated in the past in an attempt to distinguish between benign and malignant head and neck lesions.^1–4 These previous studies have been performed at 1.5T strength.^1–4 3T imaging with dedicated 16-channel head and neck coils results in substantially improved signal intensity to noise compared with 1.5T and has the potential to produce better quality DWI and ADC maps compared with conventional field strengths.However, ADC values may vary with field strength, and some authors indicate that the quantitative ADC values obtained at 1.5T may not be transferable to 3T.⁵ The purpose of our study was to determine whether ADC mapping performed at 3T with a dedicated 16-channel head and coils can differentiate between benign and malignant pathologies of the head and neck and to compare these findings with previously reported findings at 1.5T.     

Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging

BACKGROUND AND PURPOSE: Differentiating between primary cerebral lymphoma and glioblastoma multiforme (GBM) based on conventional MR imaging sequences may be impossible. Our hypothesis was that there are significant differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between lymphoma and GBM, which will allow for differentiation between them.MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 10 patients with lymphoma and 10 patients with GBM. Regions of interest were placed in only solid-enhancing tumor areas and the contralateral normal-appearing white matter (NAWM) to measure the FA and ADC values. The differences in FA and ADC between lymphoma and GBM, as well as between solid-enhancing areas of each tumor type and contralateral NAWM, were analyzed statistically. Cutoff values of FA, FA ratio, ADC, and ADC ratio for distinguishing lymphomas from GBMs were determined by receiver operating characteristic curve analysis.RESULTS: FA and ADC values of lymphoma were significantly decreased compared with NAWM. Mean FA, FA ratio, ADC (×10⁻³ mm²/s), and ADC ratios were 0.140 ± 0.024, 0.25 ± 0.04, 0.630 ± 0.155, and 0.83 ± 0.14 for lymphoma, respectively, and 0.229 ± 0.069, 0.40 ± 0.12, 0.963 ± 0.119, and 1.26 ± 0.13 for GBM, respectively. All of the values were significantly different between lymphomas and GBM. Cutoff values to differentiate lymphomas from GBM were 0.192 for FA, 0.33 for FA ratio, 0.818 for ADC, and 1.06 for ADC ratio.CONCLUSIONS: The FA and ADC of primary cerebral lymphoma were significantly lower than those of GBM. DTI is able to differentiate lymphomas from GBM.

Primary cerebral lymphoma represents 4%–7% of primary brain tumors, and its incidence has increased in the last 3 decades.¹ Despite some characteristic conventional MR imaging findings, it may be difficult or even impossible to distinguish cerebral lymphomas from glioblastoma multiforme (GBM).² Accurate preoperative differentiation between these 2 tumors is important for the determination of appropriate treatment strategies.Lymphomas are relatively hyperintense to gray matter on trace diffusion-weighted images (DWIs) and isointense to hypointense on apparent diffusion coefficient (ADC) maps, findings consistent with restricted water diffusion.^3–5 In contrast, high-grade gliomas are relatively hyperintense to gray matter on both trace DWIs and ADC maps, findings consistent with elevated diffusivity.^3,6,7 Prior studies have shown statistically significant differences in ADC between the cerebral lymphoma and GBM.^4,5 However, the GBM with restricted water diffusion, that is, hyperintense on trace images and hypointense on ADC maps, has also been reported.^8–12 Therefore, discrimination of lymphoma from some GBMs may be difficult.Diffusion tensor imaging (DTI) provides a sensitive means to detect alterations in the integrity of white matter structures.^13,14 Fractional anisotropy (FA) is a quantitative index for diffusion anisotropy that correlates with microstructural integrity of myelinated fiber tracts.^15,16 FA decreases in a wide variety of intracranial pathologies including brain tumors.^17–20 Previous studies found significant FA differences in tumors with different histologic grades or cellularity.^20–23 FA was also reported to have a strong correlation with cellularity.²⁰ Because the cellularity of lymphoma is higher than that of GBM, we hypothesized that the diffusion characteristics of lymphoma and GBM are different on DTI and will allow us to differentiate between the two.     

Preoperative grading of presumptive low-grade astrocytomas on MR imaging: diagnostic value of minimum apparent diffusion coefficient

BACKGROUND AND PURPOSE: Histopathologic grade of glial tumors is inversely correlated with the minimum apparent diffusion coefficient (ADC). We assessed the diagnostic values of minimum ADC for preoperative grading of supratentorial astrocytomas that were diagnosed as low-grade astrocytomas on conventional MR imaging.MATERIALS AND METHODS: Among 118 patients with astrocytomas (WHO grades II–IV), 16 who showed typical MR imaging findings of low-grade supratentorial astrocytomas on conventional MR imaging were included. All 16 patients underwent preoperative MR imaging and diffusion-weighted imaging. The minimum ADC value of each tumor was determined from several regions of interest in the tumor on ADC maps. To assess the relationship between the minimum ADC and tumor grade, we performed the Mann-Whitney U test. A receiver operating characteristic (ROC) analysis was used to determine the cutoff value of the minimum ADC that had the best combination of sensitivity and specificity for distinguishing low- and high-grade astrocytomas.RESULTS: Eight of the 16 patients (50%) were confirmed as having high-grade astrocytomas (WHO grades III and IV), and the other 8 patients were confirmed as having low-grade astrocytomas (WHO grade II). The median minimum ADC of the high-grade astrocytoma (1.035 × 10⁻³ mm² · sec⁻¹) group was significantly lower than that of the low-grade astrocytoma group (1.19 × 10⁻³ mm² · sec⁻¹) (P = .021). According to the ROC analysis, the cutoff value of 1.055 × 10⁻³ mm² · sec⁻¹ for the minimum ADC generated the best combination of sensitivity (87.5%) and specificity (79%) (P = .021).CONCLUSION: Measuring minimum ADC can provide valuable diagnostic information for the preoperative grading of presumptive low-grade supratentorial astrocytomas.

Despite aggressive treatments, overall prognosis of high-grade astrocytomas, especially glioblastomas, is still poor, mainly due to their infiltrative nature and high relapse rate compared with those of low-grade astrocytomas.^1–4 Accurate preoperative grading of a brain tumor is thus pivotal in choosing the treatment strategy and in the assessment of prognosis.On conventional MR imaging, malignant gliomas usually show strong contrast enhancement, peritumoral edema, mass effects, heterogeneity, central necrosis, and intratumoral hemorrhage. The typical MR imaging features of low-grade astrocytomas include a relatively well-defined usually homogeneous mass that displays little or no mass effect, with minimal or no vasogenic edema and little or no enhancement after contrast administration.^5–7 Nevertheless, it is not always easy to differentiate low-grade astrocytomas from high-grade ones on the basis of conventional MR imaging findings. It has been reported that high-grade and low-grade astrocytomas can have overlapping features on MR imaging.^2,8–12 Recently, it was shown that the histopathologic grade of glial tumors is inversely correlated with the minimum apparent diffusion coefficient (ADC).^1,3,9,13,14 Thus, we hypothesized that a high-grade astrocytoma may demonstrate a lower minimum ADC value even though it shows the typical MR imaging features of low-grade gliomas.The purpose of this study was to evaluate the diagnostic value of the minimum ADC for preoperative histopathologic grading in supratentorial astrocytomas that showed typical features of low-grade astrocytomas on conventional MR imaging.     

Apparent diffusion coefficient and cerebral blood volume in brain gliomas: relation to tumor cell density and tumor microvessel density based on stereotactic biopsies

BACKGROUND AND PURPOSE: MR imaging–based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging–based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies.MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19–78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test.RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=−0.36, P < .05), whereas no significant correlation was found between ADC and cell density.CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

Physiology-based neuroimaging techniques such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging have been used to characterize brain gliomas preoperatively. DWI assesses water diffusivity within intra- and extracellular spaces by means of apparent diffusion coefficient (ADC) measurements. Visual inspection of diffusion and ADC images has been reported as not very useful in differentiating between tumor types, whereas an important trend has appeared toward the use of quantitative diffusion imaging techniques.¹ Minimal ADC values have been reported to correlate inversely with glial and nonglial tumor cellularity as a result of the restricted diffusion of water.^2–4 ADC values have also been reported to correlate with the content of extracellular hydrophilic components of gliomas such as hyaluronan.⁵ The considerable overlap of ADC values among high- and low-grade gliomas limits their clinical use for preoperative grading.^6,7 The overlap may relate to the presence of focal necrosis within high-grade gliomas. Being focal and macroscopically undetectable, these necrotic components were not excluded from the analysis, leading to higher mean ADC values in these tumors.⁸ Thus, whether ADC values can be used as a biomarker of cellularity in gliomas should be further investigated.Dynamic susceptibility-weighted contrast-enhanced (DSC) MR imaging is widely used to study tumor angiogenesis. It provides quantification of the regional cerebral blood volume (rCBV). Increased rCBV has been related to high grade, in particular in gliomas of astrocytic origin.^9–15 Clinically, DSC imaging has been successfully used not only for better characterization of brain tumors but also for tumor-recurrence detection. Thus, inclusion of this technique is recommended in diagnostic and follow-up MR imaging protocols for brain tumors. Correlations between maximal rCBV values and microvessel density and vascular endothelial growth factor have been previously reported in gliomas.^11–14 Still, rCBV cannot be considered as a valid biomarker of local tumor angiogenesis on the sole basis of studies reporting maximal rCBV values in the whole tumor. Gliomas are highly heterogeneous tumors with areas of low- and high-grade frequently coexisting within a single mass. In fact, this heterogeneity has prompted the targeting of biopsies by functional imaging techniques, such as positron-emission tomography (PET), which are usually coregistered to the high-resolution anatomic MR images.^16–18To study how image-based variables such as ADC and rCBV relate to histology, one must recognize the heterogeneity of gliomas, to compare these measurements locally to the corresponding histologic samples. Stereotactic biopsies of brain tumors guided by imaging techniques provide the ideal sample to apply this strategy.The purpose of this study was to correlate regionally ADC and rCBV values with cell and microvessel densities in gliomas, by using coregistered MR imaging and stereotactic biopsies.     

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.     

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.     

In vivo differentiation of aerobic brain abscesses and necrotic glioblastomas multiforme using proton MR spectroscopic imaging

BACKGROUND AND PURPOSE: Abscesses caused by aerobic bacteria (aerobic abscesses) can simulate intracranial glioblastomas multiforme (GBMs) in MR imaging appearance and single voxel (SV) proton MR spectroscopy of the central cavity. The purpose of our study was to determine whether MR spectroscopic imaging (SI) can be used to differentiate aerobic abscesses from GBMs. Our hypothesis was that metabolite levels of choline (Cho) are decreased in the ring-enhancing portion of abscesses compared with GBMs.MATERIALS AND METHODS: Fifteen patients with aerobic abscesses were studied on a 1.5T MR scanner using an SV method and an SI method. Proton MR spectra of 15 GBMs with similar conventional MR imaging appearances were used for comparison. The resonance peaks in the cavity, including lactate, cytosolic amino acids, acetate, succinate, and lipids, were analyzed by both SV MR spectroscopy and MRSI. In the contrast-enhancing rim of each lesion, peak areas of N-acetylaspartate (NAA), choline (Cho), lipid and lactate (LL), and creatine (Cr) were measured by MRSI. The peak areas of NAA-n, Cho-n, and Cr-n in the corresponding contralateral normal-appearing (-n) brain were also measured. Maximum Cho/Cr, Cho/NAA, LL/Cr-n, and Cho/Cho-n and minimum Cr/Cr-n and NAA/NAA-n ratios in abscesses and GBMs were compared using the Wilcoxon rank sum test. After receiver operating characteristic curve analysis, diagnostic accuracy was compared.RESULTS: Cytosolic amino acid peaks were found in the cavity in 7 of 15 patients with aerobic abscesses. Means and SDs of maximum Cho/Cr, Cho/NAA, LL/Cr-n, and Cho/Cho-n and minimum Cr/Cr-n and NAA/NAA-n ratios were 3.38 ± 1.09, 3.88 ± 2.13, 2.72 ± 1.45, 1.98 ± 0.53, 0.53 ± 0.16, and 0.44 ± 0.09, respectively, in the GBMs, and 1.77 ± 0.49, 1.48 ± 0.51, 2.11 ± 0.67, 0.81 ± 0.21, 0.48 ± 0.2, and 0.5 ± 0.15, respectively, in the abscesses. Significant differences were found in the maximum Cho/Cr (P = .001), Cho/NAA (P = .006), and Cho/Cho-n ratios (P < .001) between abscesses and GBMs. Diagnostic accuracy was higher by Cho/Cho-n ratio than Cho/Cr and Cho/NAA ratios (93.3% versus 86.7% and 76.7%).CONCLUSION: Metabolite ratios and maximum Cho/Cho-n, Cho/Cr, and Cho/NAA ratios of the contrast-enhancing rim were significantly different and useful in differentiating aerobic abscesses from GBMs by MRSI.

Brain abscess can be a lethal condition if appropriate treatment is delayed. Thus, early diagnosis of brain abscess is desired and is a challenge for clinicians and radiologists. Radiologically, a brain abscess in the capsule stage appears in CT and in MR imaging as an expansile, rim-enhancing mass surrounded by edema, which is similar in appearance to necrotic malignant tumors, especially glioblastoma multiforme (GBM).^1,2 Clinically, both brain abscesses and GBMs may cause nonspecific headaches in the absence of fever, focal neurologic deficits, epileptic seizures, and disturbances in higher-level cortical function. In addition, laboratory examination often shows normal white blood cell count.^1,2 Further reduction of mortality from brain abscesses requires more rapid, accurate, and safe diagnostic techniques. Application of diffusion-weighted imaging (DWI) in distinguishing between pyogenic brain abscesses and cystic or necrotic brain tumors has been reported to be useful in many publications.^3–8 The cystic or necrotic portion of tumors almost always has a low signal intensity on DWI and a higher apparent diffusion coefficient (ADC) value; however, some exceptions have been reported for necrotic brain tumors.^7–12 Hyperintensity with restricted diffusion is diagnostic, but not pathognomonic, for pyogenic abscess on DWI. However, exceptions of DWI studies and substantial variability in the ADCs have been reported for pyogenic abscesses.^8,12–16Single-voxel proton MR spectroscopy of the central cystic portion has been reported to allow the broad group of pyogenic abscesses to be distinguished from malignant gliomas.^17–22 Acetate, succinate, and amino acids have been identified in cerebral abscesses in humans and were used as bacterial marker metabolites for noninvasive diagnosis by MR spectroscopy.^17–22 Abscesses caused by anaerobic bacteria have been distinguished from those caused by aerobic bacteria based on metabolites detectable with MR spectroscopy (acetate and succinate).^21–23 However, spectral patterns recorded for the cystic or necrotic components of GBMs and abscesses caused by aerobic bacteria (aerobic abscesses) were similar by single-voxel MR spectroscopy.^18,21,24 Diagnosis based on such subjectively selected metabolites or metabolite ratios was not possible.²⁴At pathologic examination, the enhancing rim of GBMs represents infiltrating tumor cells,^25,26 and an increased Cho/Cr ratio was observed. Pathologically, the enhancing rim of a pyogenic abscess represents an inflammatory infiltrate composed of neutrophils and, later, macrophages and lymphocytes. Granulation tissue surrounds the area of inflammation and eventually develops into a fibrous capsule. This capsule, in turn, is surrounded by gliotic, edematous brain tissue. In the experimental setting, brain abscesses have been shown to have relatively high amounts of mature collagen and decreased neovascularity.^27,28 The Cho/Cr ratio of rim-enhancing lesion of abscesses would be presumed to be less than that of GBMs.Recent developments in MR spectroscopy have made it possible to obtain spectroscopic MR imaging with high spatial resolution and multiple spectra simultaneously from contiguous voxels.^29,30 To date, proton MR spectroscopic imaging has not been used to differentiate aerobic abscesses from GBMs. We aimed to test the feasibility of MR spectroscopic imaging to distinguish between aerobic abscesses and GBMs by the evaluation of the contrast-enhancing rim of the lesions. Our hypothesis was that metabolite levels of Cho are decreased in the rim-enhancing portion of aerobic abscesses relative to the Cho seen in the rim-enhancing portion of necrotic GBMs.     

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.     

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.     

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.     

T1 signal intensity and height of the anterior pituitary in neonates: correlation with postnatal time

BACKGROUND AND PURPOSE: The anterior pituitary of a term neonate is usually hyperintense on T1-weighted MR images, which may represent histologic changes of the gland due to the effect of high estrogen levels during the fetal period; however, MR findings of a preterm neonate have not been fully evaluated. The purpose of this study was to investigate whether intensity and size of the neonatal anterior pituitary on MR images obtained near term of corrected age correlates with the gestational age at birth or postnatal time.MATERIALS AND METHODS: Data of 88 consecutive neonates (gestational age, 24–41 weeks; mean, 31.5 weeks) were analyzed. All of the neonates underwent MR imaging at a corrected age of 0 months ± 4 weeks. Relative signal intensity of the anterior pituitary compared with that of the pons on T1-weighted sagittal images was calculated. Height of the pituitary was also measured. Stepwise regression analysis was performed to evaluate the effects of gestational age at birth and postnatal time on the relative signal intensity and on the pituitary height.RESULTS: The relative signal intensity significantly negatively correlated with postnatal time (P = .001) but not with gestational age at birth (P = .42). Pituitary height significantly negatively correlated with postnatal time (P = .049) but not with gestational age at birth (P = .071).CONCLUSION: A significant negative correlation exists between postnatal time and signal intensity on T1-weighted MR images of the anterior pituitary obtained near term. A nonhyperintense anterior pituitary is a normal MR finding of preterm neonates when imaged near term.

Several MR studies have revealed changes in size, shape, and intensity of the neonatal anterior pituitary gland.^1–5 The anterior pituitary usually shows bright signal intensity on T1-weighted MR images in term neonates.^1–3 This bright signal intensity is known to be seen only in early infancy and begin to disappear from approximately 2 months after birth.^2,3 After the first few months, the gland displays the appearance of an adult gland.^1–3,6 To the best of our knowledge, MR findings of a preterm neonate have not been fully evaluated.Several histologic analyses of the human fetal anterior pituitary gland have been reported.^7–9 Asa et al⁷ reported that, after gestational week 25, the most significant change in histology of the anterior pituitary is an increase in prolactin-containing cells. van Nesselrooij et al¹⁰ clarified that the pituitary of a rat that had received estrogen developed hyperplasia of prolactin cells, and MR imaging detected enlargement of the gland.¹⁰ Kovacs and Horvath¹¹ stated that, due to the effect of maternal estrogen, prolactin cells are numerous in the fetus and neonate, decreasing after birth and remaining low during childhood. These reports suggest that estrogen may be 1 of the key hormones in maturation of the anterior pituitary gland in pregnancy.The placenta is the principal source of increases in steroids, estrogens, and progesterone during pregnancy.^12,13 From the perspective of the period under the effect of estrogen produced by placenta, some histologic differences in the anterior pituitary may present due to the duration of pregnancy.We hypothesized that gestational age at birth and intensity of the anterior pituitary on MR images obtained near term of corrected age may be positively correlated and/or that postnatal time (elapsed time between birth and the MR examination) and intensity of the anterior pituitary may be negatively correlated, because neonates with a shorter gestational period have a shorter period under the effects of estrogen during the fetal period and a longer period after removal of the influence of placental estrogen. The purpose of this study was to reveal whether intensity and size of the neonatal anterior pituitary on MR images obtained near term of corrected age correlates with the gestational age at birth or postnatal time.     

High b-value diffusion tensor imaging of the neonatal brain at 3T

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging studies of the adult brain have shown that contrast between lesions and normal tissue is increased at high b-values. We designed a prospective study to test the hypothesis that diffusion tensor imaging (DTI) obtained at high b-values increases image contrast and lesion conspicuity in the neonatal brain.MATERIALS AND METHODS: We studied 17 neonates, median (range) age of 10 (2–96) days, who were undergoing MR imaging for clinical indications. DTI was performed on a Philips 3T Intera system with b-values of 350, 700, 1500, and 3000 s/mm². Image contrast and lesion conspicuity at each b-value were visually assessed. In addition, regions of interest were positioned in the central white matter at the level of the centrum semiovale, frontal and occipital white matter, splenium of the corpus callosum, posterior limb of the internal capsule, and the thalamus. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values for these regions were calculated.RESULTS: Isotropic diffusion image contrast and lesion-to-normal-tissue contrast increased with increasing b-value. ADC values decreased with increasing b-value in all regions studied; however, there was no change in FA with increasing b-value.CONCLUSIONS: Diffusion image contrast increased at high b-values may be useful in identifying lesions in the neonatal brain.

Diffusion-weighted MR imaging is increasingly being used to investigate neonatal cerebral pathologic lesions. Previous studies have shown that diffusion-weighted imaging (DWI) is able to demonstrate lesions that are not always discernible on conventional MR imaging, and the usefulness of this imaging technique to assess infarction^1-3 and metabolic disorders^4,5 in the neonatal brain is established. In addition to the qualitative assessment of injury, diffusion tensor imaging (DTI) provides directionally invariant measurements of mean diffusivity and diffusion anisotropy. These objective measurements provide information regarding water molecular mobility, which reflect tissue microstructure and thereby provide insight into mechanisms of brain development and disease processes.Diffusion-weighted MR imaging with b-values of more than 2000 s/mm² has been performed in animal studies,^6,7 in the adult brain,^8-14 and in infants.^8,15 These studies suggest that diffusion contrast characteristics are altered at higher b-values. In addition, adult studies of cerebral infarction¹³ and white matter disease¹⁴ have shown increased lesion conspicuity at higher b-values, and so it is possible that high b-value DTI in neonates may also improve lesion conspicuity.To our knowledge, the only studies investigating the effects of high b-value diffusion imaging in the neonatal brain were done on infants whose results on conventional MR imaging was considered normal and did not examine the full diffusion tensor.^8,15 In this prospective study, we tested the hypothesis that diffusion imaging at high b-values enhances contrast between lesions and normal tissue in neonates and thereby increases lesion conspicuity. Furthermore, we acquired diffusion data in 6 noncollinear directions of sensitization, enabling us to examine the effects of high b-values on diffusion anisotropy.The aims of this study were 1) to assess isotropic DWI contrast and lesion conspicuity at b-values between 350 and 3000s/mm² and 2) to assess whether apparent diffusion coefficient (ADC) or fractional anisotropy (FA) in the neonatal brain change with increasing b-value.     

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.     

Sinonasal inverted papilloma: value of convoluted cerebriform pattern on MR imaging

BACKGROUND AND PURPOSE: A convoluted cerebriform pattern (CCP) has been reported as a valuable MR imaging feature of inverted papilloma (IP). The purpose of this study was to validate the usefulness of CCP for distinguishing IP from various malignant sinonasal tumors in a relatively large number of patients.MATERIALS AND METHODS: We retrospectively reviewed MR images of 30 patients with IP and 128 patients with various malignant sinonasal tumors proved on histologic examination and compared the prevalence of a CCP between the 2 groups. In 8 patients with IP concomitant with squamous cell carcinoma, we also tried to find the MR features to help suggest coexistent malignancy.RESULTS: A CCP was demonstrated in all 30 (100%) of the IPs and 17 (13%) of the 128 malignant sinonasal tumors on MR imaging. There was a significant statistical difference in the prevalence of a CCP between IP and malignant sinonasal tumors with the overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy 100%, 87%, 64%, 100%, and 89%, respectively. Of 8 IPs concomitant with squamous cell carcinoma, a focal loss of a CCP was demonstrated in 4 tumors, 3 of which also showed aggressive bone destruction with extrasinonasal extension on MR images.CONCLUSION: Although a CCP is a reliable MR imaging feature of sinonasal IPs, it can also be seen in various malignant sinonasal tumors. A focal loss of a CCP might be a clue to the diagnosis of IPs concomitant with malignancy.

Inverted papilloma (IP) is an uncommon benign epithelial tumor of the sinonasal tract, accounting for 0.5% to 4.0% of primary nasal tumors.^1,2 Although benign, it has a known propensity for a high rate of recurrence, local aggressiveness, multicentricity, and association with synchronous or metachronous squamous cell carcinoma (SCC).^3-12 Although CT and MR imaging are useful for preoperative assessment of sinonasal IP, differentiation of IP from other malignant sinonasal tumors is often difficult because of a significant overlap of the imaging features.^13-19Barnes et al²⁰ described a distinctive gross mucosal morphology of IP, a so-called convoluted cerebriform pattern (CCP), which can be reflected on MR imaging by the characteristic alternating hypointense and hyperintense bands on T2-weighted and contrast-enhanced T1-weighted images, as reported by Ojiri et al¹⁷ and supported by Maroldi et al¹⁹ years later. It would be useful for planning therapeutic strategies if the CCP on MR imaging can suggest the preoperative diagnosis of IP, because more aggressive surgical approaches would be needed for IPs concomitant with SCC and other malignant sinonasal tumors. However, one previous study reported by Yousem et al¹³ failed to find this sign as a specific MR imaging finding to diagnose IP. The purpose of this study was to evaluate the diagnostic accuracy of a CCP depicted on MR imaging for distinguishing IP from other malignant sinonasal tumors in a relatively large number of patients.     

Late evaluation of silent cerebral ischemia detected by diffusion-weighted MR imaging after filter-protected carotid artery stenting

BACKGROUND AND PURPOSE: Postoperative diffusion-weighted MR imaging (DWI) often discloses new lesions after carotid artery stent placement (CAS), most of them asymptomatic. Our aim was to investigate the fate of these silent ischemic lesions.MATERIALS AND METHODS: We prospectively studied 110 patients undergoing protected transfemoral CAS, 98 of whom underwent DWI before and after the intervention. Patients in whom DWI disclosed silent postoperative lesions also had delayed MR imaging. Preoperative, postoperative, and delayed scans were compared.RESULTS: Of the 92 patients without postoperative symptoms, DWI disclosed 33 new silent ischemic lesions in 14 patients (15.2%), 13 of whom (30 lesions) underwent delayed MR imaging after a mean follow-up of 6.2 months. In 8 of these 13 patients (61%), MR imaging disclosed 12 persistent lesions (12/30, 40%). The reversibility rate depended significantly on the location (cortical versus subcortical) and size (0–5 versus 5–10 mm) of the lesions (P < .05 by χ² test).CONCLUSIONS: Because many silent ischemic lesions seen on postoperative DWI after CAS reverse within months, the extent of permanent CAS-related cerebral damage may be overestimated.

Carotid artery stent placement (CAS) is today considered in many centers a valid alternative to carotid surgery for treating carotid artery stenosis because it achieves stroke and death rates matching those after surgery.^1,2Despite widespread use of cerebral protection systems in patients undergoing endovascular carotid interventions,^3,4 diffusion-weighted MR imaging (DWI) of the brain, currently the most effective tool for diagnosing acute cerebral ischemia,^5,6 detects a high incidence of asymptomatic ischemic lesions after CAS, ranging from 21% to 54% for unprotected procedures^7,8 and from 21% to 40% for protected procedures.^9–13 Few studies have described the late outcome of early postoperative DWI lesions.^14–16 Whether these silent ischemic lesions cause permanent brain damage with cognitive impairment or merely transient ischemia without sequelae remains unclear.In this prospective study, to investigate the extent of permanent cerebral ischemic damage in patients undergoing protected CAS, we used postoperative DWI and delayed MR imaging to assess the outcome (patient and lesion reversibility rates) of asymptomatic ischemic lesions after CAS and studied factors potentially influencing reversibility.     

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.     

Tumor-volume changes after radiosurgery for vestibular schwannoma: implications for follow-up MR imaging protocol

BACKGROUND AND PURPOSE: The outcome of radiosurgery for vestibular schwannoma (VS) is assessed by posttreatment measurement of tumor size and could be influenced by the timing and quality of the assessment. This study evaluates the volumetric changes of VS after radiosurgery and proposes a radiologic follow-up program.MATERIALS AND METHODS: Of 142 patients with VS treated with radiosurgery, we selected patients who were followed at least 3 times during a minimum of 32 months with a T1-weighted gadolinium-enhanced high-resolution 3D MR imaging examination identical to the pretreatment MR imaging. Forty-five patients were identified with a mean follow-up of 50 months (range, 32–78 months). Pre- and posttreatment tumor volumes were calculated by using BrainSCAN software by manually contouring tumors on each MR imaging study. Volume changes of >13% were defined as events.RESULTS: At last follow-up MR imaging, volumes were smaller in 37 (82.2%) of the 45 patients. Eleven (29.7%) of these 37 tumors showed transient swelling preceding regression, with a median time to regression of 34 months (range, 20–55 months). Seven (15.6%) of the 45 tumors had volume progression compared with the tumor on pretreatment MR imaging studies. Of these 7 tumors, 3, however, had volume regression compared with the preceding MR imaging study, and in 4, volume progression was ongoing. One tumor remained the same.CONCLUSIONS: Tumor-volume measurements by standardized T1-weighted gadolinium-enhanced high-resolution 3D MR imaging follow-up protocols revealed good local control of VS after radiosurgery. The first-follow-up MR imaging at 2 years and the second at 5 years postradiosurgery differentiated transient progression from ongoing progression and may prevent unnecessary therapeutic interventions.

Vestibular schwannoma (VS), also known as acoustic neuroma or acoustic neurinoma, is a benign tumor in the cerebellopontine angle, which arises from Schwann cells forming the myelin sheath around the vestibulocochlear nerve. It may cause symptoms due to compression effects. These symptoms include unilateral hearing loss, facial and trigeminal nerve dysfunction, and eventually hydrocephalus. Surgical removal of VS has long been the treatment of choice. Although treatment-related mortality has dropped to <1%, serious side effects have been reported, including unilateral deafness, facial nerve pareses, and CSF leakage.^1–5Leksell⁶ first described radiosurgery in 1971 as an alternative treatment for patients with VS. With the introduction of CT and MR imaging, this treatment has become more popular in the past decade, and treatment-related toxicity seems to be less compared with that in surgery.^5,7,8 The aim of radiosurgery for VS is tumor control (ie, arrest of further increase of tumor volume). This means that treatment outcome has to be assessed by measurement of tumor size rather than with surgical removal. Most publications on treatment outcome in radiosurgery of VS report maximal tumor diameter as a criterion of assessing local control.^9–14 Tumor-volume calculations, based on perpendicular tumor diameters, as described by the American Academy of Otolaryngology-Head and Neck Surgery, have been found to be more adequate in the assessment of local control.¹⁵ Improvements in the quality of MR imaging and the availability of digital data in recent years, however, enable measurement of tumor volume more accurately. Publications on measured tumor-volume outcome after radiosurgery for VS, however, are scarce and report voxel-based volume measurements, which are only applicable with small intracanalicular VS, or report volume measurements based on tumor contour drawings on hard copies and drawings on CT scans, or do not use uniform imaging techniques.^16–18Because local tumor control is always defined at a certain time interval after treatment, some authors published tumor size at different time points after radiosurgery, based on tumor diameter.^19–21 The few studies that are available on these tumor-size time trends based on actual tumor-volume measurements have follow-up periods that are generally too short to assess long-term tumor-size time trends.^17,18To describe actual tumor-volume changes in VS treated with radiosurgery and subsequently to propose a post-treatment follow-up MR imaging program, we performed a retrospective study in which we measured and analyzed long-term tumor-volume changes based on digital tumor contour drawings on T1-weighted gadolinium-enhanced high-resolution 3D MR imaging in patients treated with radiosurgery for VS.