Optimal diffusion-weighted imaging protocol for lesion detection in transient global amnesia

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) can depict small punctate hyperintense lesions in the hippocampus in transient global amnesia (TGA). The purpose of this study was to find an optimal DWI protocol for lesion detection in TGA by investigating various imaging parameters and imaging timing after symptom onset.MATERIALS AND METHODS: Sixteen patients with TGA diagnosed during 14 months underwent DWI within 24 hours and again at follow-up 3 days after onset. Each DWI session included 4 different sequences using different b-values (seconds per square millimeter) and section thicknesses (millimeter): 1000/5, 1000/3, 2000/3, and 3000/3. The presence or absence of hyperintense lesions on the 8 DWIs was determined visually, and the number of lesions detected was compared.RESULTS: Thirteen of the 16 patients (81%) had either single or multiple punctate hyperintense lesions, totaling 24 lesions, and the remaining 3 patients had no lesions. All lesions detected were in the hippocampus except 1. The number of lesions detected on initial DWIs at a b-value/section thickness of 1000/5, 1000/3, 2000/3, and 3000/3 was 3, 9, 13, and 13, respectively, whereas that of follow-up DWIs was 17, 22, 24, and 24, respectively.CONCLUSION: On the basis of these preliminary results, the highest lesion detection was achieved for DWI with b = 2000/3 mm or b = 3000/3 mm at 3 days postonset. When no lesion is detected by DWI within 24 hours after onset, follow-up DWI is recommended several days later.

Transient global amnesia (TGA) is clinically defined as sudden onset anterograde amnesia with preserved alertness, attention, and personal identity, which occurs during a period of no more than 24 hours with no long-term sequelae.^1–3 The incidence of TGA has been reported to be 5–11 per 100,000 persons per annum.^2,4,5 The etiology and pathogenesis of TGA are uncertain, though several different causes are suggested, such as ischemia, migraine, epileptic seizure, venous congestion, and psychological disturbances.⁶Recent diffusion-weighted imaging (DWI) studies have indicated the presence of focal hyperintensities involving the hippocampus in TGA.^7–11 The lesions detected by DWI are small and punctate (1–3 mm) and located within the lateral portion of the hippocampus.^9,11,12 Since Strupp et al¹³ first detected hyperintense lesions in the hippocampus in TGA by using DWI, the frequency of lesions detected on DWI has been reported in a range of 0%–84%.^9,10,14,15 According to a recent study, this discrepancy in detection rates appears to be attributable to the different timing of imaging from the onset of symptoms.⁹ In this previous study, a detection rate of only 6% by DWI was achieved within several hours of symptom onset, but this increased up to 84% at 48 hours post-symptom onset.DWI parameters, such as b-value and section thickness, might also importantly influence the detection rate of the lesions. In particular, b-values higher than 1000 s/mm² might increase the ability of DWI to detect subtle diffusion restrictions caused by small lesions. Moreover, section thicknesses of <5 mm may also increase the detection rate of small punctate lesions by decreasing partial volume averaging effects. However, optimal DWI parameters for lesion detection have not been studied previously. The purpose of the present study was to find an optimal DWI protocol for lesion detection by investigating b-values, section thickness, and imaging timing after symptom onset.     

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.     

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.     

Role of perfusion CT in glioma grading and comparison with conventional MR imaging features

BACKGROUND AND PURPOSE: Perfusion imaging using CT can provide additional information about tumor vascularity and angiogenesis for characterizing gliomas. The purpose of our study was to demonstrate the usefulness of various perfusion CT (PCT) parameters in assessing the grade of treatment-naïve gliomas and also to compare it with conventional MR imaging features.MATERIALS AND METHODS: PCT was performed in 19 patients with glioma (14 high-grade gliomas and 5 low-grade gliomas). Normalized ratios of the PCT parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], normalized mean transit time [nMTT]) were used for final analysis. Conventional MR imaging features of these tumors were assessed separately and compared with PCT parameters. Low- and high-grade gliomas were compared by using the nonparametric Wilcoxon 2-sample tests.RESULTS: Mean nCBV in the high- and low-grade gliomas was 3.06 ± 1.35 and 1.44 ± 0.42, respectively, with a statistically significant difference between the 2 groups (P = .005). Mean nCBF for the high- and low-grade gliomas was 3.03 ± 2.16 and 1.16 ± 0.36, respectively, with a statistically significant difference between the 2 groups (P = .045). Cut points of >1.92 for nCBV (85.7% sensitivity and 100% specificity), >1.48 for nCBF (71.4% sensitivity and 100% specificity), and <1.94 for nMTT (92.9% sensitivity and 40% specificity) were found to identify the high-grade gliomas. nCBV was the single best parameter; however, using either nCBV of >1.92 or nCBF of >1.48 improved the sensitivity and specificity to 92.9% and 100%, respectively. The sensitivity and specificity for diagnosing a high-grade glioma with conventional MR imaging were 85.7% and 60%, respectively.CONCLUSIONS: PCT can be used for preoperative grading of gliomas and can provide valuable complementary information about tumor hemodynamics, not available with conventional imaging techniques. nCBV was the single best parameter correlating with glioma grades, though using nCBF when nCBV was <1.92 improved the sensitivity. An nCBV threshold of >1.92 was found to identify the high-grade gliomas.

Gliomas, the most common primary brain neoplasms in adults, are very heterogeneous tumors. High-grade gliomas can be highly invasive and extremely vascular tumors.Glioma grading is currently based on the histopathologic assessment of the tumor, which is achieved by stereotactic brain biopsy or cytoreductive surgery; and there are inherent limitations with these techniques and their interpretation.¹ Therapeutic approaches, response to therapy, and prognosis depend on accurate grading, and thus finding the part of the tumor with the highest grade to be biopsied is critical.Conventional MR imaging has a limited role in differentiating gliomas because contrast-enhanced images reveal disrupted or absent blood-brain barrier and not necessarily microvascularity or neovascularity of the tumoral lesion.^2,3 The 2 most important factors in determining the malignancy of gliomas is their ability to infiltrate the brain parenchyma and to recruit or synthesize vascular networks for further growth.⁴Malignant brain tumors are characterized by neovascularity and increased angiogenic activity, with a higher proportion of immature and hyperpermeable vessels.^5,6 Because vascular proliferation is an important characteristic in the grading of astrocytomas,⁷ imaging techniques that provide hemodynamic information about the tumor may help in characterizing glioma malignancy, which may overcome some of the limitations of histopathologic sampling error and conventional MR imaging. Perfusion imaging has been useful in grading cerebral neoplasms^8–14 and may provide reliable information on tumor physiology such as microvascularity, angiogenesis, micronecrosis, and cellularity.Perfusion imaging of brain tumors has shown that certain cerebral perfusion parameters such as regional blood volume and blood flow correlate well with tumor grade, and it has also been helpful in distinguishing recurrent tumor from radiation necrosis.^3,15Most of the prior perfusion studies comparing histologic features with perfusion parameters have used various MR perfusion techniques.^3,15 However, recently perfusion CT (PCT) has been used as an alternative method in assessing cerebral hemodynamics for stroke and brain tumors.¹⁶ PCT allows measurement of tumor vascular physiology, and maps of tumor blood flow, blood volume, mean transit time (MTT), and permeability–surface area product can be generated. In view of the wider availability, faster scanning times, and low cost combined with its ease of quantification of various perfusion parameters as compared with MR perfusion, PCT is potentially well suited to studying brain tumors and monitoring tumor response to antiangiogenic agents.¹⁶The purpose of our study was to demonstrate the usefulness of various PCT parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and MTT in assessing the grade of treatment-naïve gliomas and also to compare them with conventional MR features.     

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.     

Histogram analysis of MR imaging-derived cerebral blood volume maps: combined glioma grading and identification of low-grade oligodendroglial subtypes

BACKGROUND AND PURPOSE: Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR perfusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity (LOH) on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors.MATERIALS AND METHODS: Fifty-two patients (23 women, 29 men; mean age, 52 years; range, 19–78 years) with histologically confirmed gliomas were imaged by using dynamic susceptibility contrast MR imaging at 1.5T. Relative cerebral blood volume (rCBV) maps were created, and 4 neuroradiologists defined the glioma volumes independently. Averaged over the 4 observers, a histogram-analysis method was used to assess the normalized histogram peak height of the glioma rCBV distributions.RESULTS: Of the 52 patients, 22 had oligodendroglial tumors. The histogram method was able to differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) (Mann-Whitney U test, P < .001) and to identify low-grade oligodendroglial subtypes (P = .009). The corresponding intraclass correlation coefficients were 0.902 and 0.801, respectively. The sensitivity and specificity in terms of differentiating low-grade oligodendroglial tumors without LOH on 1p/19q from the other tumors was 100% (6/6) and 91% (42/46), respectively.CONCLUSION: With histology as a reference, our results suggest that histogram analysis of MR imaging–derived rCBV maps can differentiate HGGs from LGGs as well as low-grade oligodendroglial subtypes with high interobserver agreement. Also, the method was able to identify low-grade oligodendroglial tumors without LOH on 1p/19q in a population of patients with astrocytic and oligodendroglial tumors.

MR imaging is the technique of choice to characterize brain tumor malignancy before treatment, with dynamic susceptibility contrast perfusion imaging as a widely used imaging technique for tumor grading.^1–8 Using the WHO histopathologic criteria,⁹ we refer to glioma grades I–II to as low-grade gliomas (LGGs), whereas grades III-IV are referred to as high-grade gliomas (HGGs). Differentiation of HGGs from LGGs by MR imaging is based on the higher relative cerebral blood volume (rCBV) values of HGGs compared with LGGs. Image-based glioma grading is currently performed by assessing the maximal ratio between a rCBV area within the glioma and an unaffected contralateral rCBV value (rCBV_max, “hot-spot” method). A well-known problem with this method is that most oligodendroglial tumors (oligodendrogliomas or oligoastrocytomas) exhibit higher rCBV_max values than astrocytomas irrespective of glioma grade.^1,7 A reason for this might be that most oligodendroglial tumors are located in cortical areas and have direct involvement with gray matter.¹⁰ Also, it has been suggested that the degree of oligodendroglial vascularity is associated with loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), seen in 40%–90% of oligodendroglial tumors.^11,12 Most (∼90%) oligodendroglial tumors with LOH on 1p/19q are known to have “classic histopathologic” features.¹³An oligodendroglial tumor can be defined as having classic histopathologic features if >50% of the tumor area exhibits uniform round nuclei with perinuclear halos.^12,14 Such tumors often have an attenuated network of branching capillaries resembling a “chicken wire” pattern.¹² Recent studies have reported that rCBV_max measurements by using the hot-spot method might be predictive of 1p/19q status, showing that oligodendroglial tumors with LOH on 1p/19q have significantly higher rCBV_max values than oligodendroglial tumors without LOH on 1p/19q.^15,16 However, on the basis of the rCBV_max values, there was no significant difference between HGGs and LGGs in either study. Because oligodendroglial tumors constitute ∼10% of all diffuse gliomas (astrocytic and oligodendroglial tumors),^11,17,18 it would represent a major limitation to the hot-spot method if these tumors had to be characterized by other diagnostic techniques. Little focus has been placed on whether the distribution of rCBV values in low-grade oligodendroglial tumors is more homogeneous than that in HGGs, irrespective of genotype. If so, a more rigorous grading method based on histogram analysis^19,20 might differentiate between oligodendroglial subtypes without losing the ability to differentiate between HGGs and LGGs.Patients diagnosed with low-grade oligodendroglial tumors with LOH on 1p/19q have been shown to respond more favorably to treatment and have prolonged survival rates compared with patients without this genotype.^21,22 Hence, patients diagnosed with low-grade oligodendroglial tumors without LOH on 1p/19q are expected to have a reduced response to treatment and may, therefore, require a more aggressive treatment plan. To date, few studies have identified clear correlations between oligodendroglial subtype, tumor growth, and conventional MR imaging features. One study reported, however, that oligodendroglial tumors with indistinct/irregular borders, as seen on conventional MR images, were more likely to have LOH on 1p/19q compared with tumors with sharp/smooth borders.²³ Unfortunately, these findings were not related to glioma grade. Although perfusion MR imaging is considered a good technique for grading gliomas, little focus has been placed on whether perfusion MR imaging can identify low-grade oligodendroglial subtypes in a population of patients with astrocytic and oligodendroglial tumors.In view of the above, the purpose of our study was twofold: first, to assess retrospectively whether a histogram analysis method of perfusion MR images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without LOH on 1p/19q; and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors.     

Reproducibility, interrater agreement, and age-related changes of fractional anisotropy measures at 3T in healthy subjects: effect of the applied b-value

BACKGROUND AND PURPOSE: There is no reproducibility study of fractional anisotropy (FA) measurements at 3T using regions of interest (ROIs). Our purpose was to establish the extent and statistical significance of the interrater variability, the variability observed with 2 different b-values, and in 2 separate scanning sessions.MATERIALS AND METHODS: Twelve healthy volunteers underwent MR imaging twice. MR imaging was performed on a 3T unit, and FA maps were analyzed independently by 2 observers using ROIs positioned in the corpus callosum, internal capsules, corticospinal tracts, and right thalamus. Changes in FA values (×10³) measured with 2 b-values (700 and 1000 s/mm²), age-related differences, interobserver agreement, and measurement reproducibility were assessed.RESULTS: In the right internal capsule genu (FA = 702/728; b = 1000/700 s/mm²) and the left anterior limb of the internal capsule (AIC; FA = 617/745; b = 1000/700 s/mm²), the FA values were significantly different between the 2 b-values (P = .02 and .05, respectively). Significant age-related differences in FA were observed in the genu of the corpus callosum and in the left AIC. Interrater measurements showed fair-to-moderate agreement for most anatomic structures. The lowest significant change for a single subject regarding any FA values between the 2 sessions was in the corpus callosum (4%), whereas the highest one was in the corticospinal tracts (27%). The Bland-Altman plot analysis showed that the 1000-s/mm² b-value gave satisfactorily reproducible measurements equally good or better than the 700-s/mm² b-value.CONCLUSION: The reproducibility of FA estimates using ROIs was satisfactory. Measurements with a b-value at 1000 s/mm² showed superior reproducibility in most anatomic locations.

Diffusion tensor imaging (DTI) refers to a group of MR imaging techniques for investigating the water mobility (diffusion) and microstructure, as well as organization of different tissues in relation to directionality of diffusion.¹ In the case of the brain tissue, the water mobility is not equal in all directions (isotropic) but greater in one direction than another (anisotropic). This anisotropy is usually expressed by 2 metrics: trace and fractional anisotropy (FA). The trace represents the total measured diffusion, whereas the FA quantifies the degree to which a single diffusion orientation is dominant by measuring related coherence within a voxel. Initial evidence for use of this technique has been demonstrated in brain maturation and aging, in demyelinating disorders, in stroke, in brain tumors, and in brain trauma.^2–9Because DTI is increasingly becoming included in standard clinical MR imaging protocols, the reliability of DTI measurements is an important concern that is related to the stability of the equipment parameters and examination conditions and, perhaps, even true variations in the measurements over time. Initial evidence showed more pronounced variability of FA across different scanners than across similar sequences on the same scanner.¹⁰ Under the assumption of a stable examination environment, the next serious concern is the availability of normative data that are essential for the interpretation of pathologic findings.^8,11 Normative DTI data have been acquired for infants, children, and adolescents in a narrow, as well as in a wider, age interval.^12–15 The aforementioned studies are widely performed on 1.5T MR imaging scanners (whereas 3T systems are increasingly available) and use a voxelwise method for FA analysis. However, voxelwise analysis requires intersubject registration and smoothing, which may be a source of errors in the acquired FA values.The reproducibility of the quantitative FA is essential to detect changes in the white matter of patients during the follow-up of longitudinal DTI studies. In this case, any changes associated with certain pathology or aging can be attributed to the evolving disease or aging and be separated from the usual values of deviation and variability that characterize any repeated measurements.^16,17 To our knowledge, the evidence of DTI reproducibility on 3T units in adults is limited and investigated a narrow range of age by using a voxel-to-voxel analysis.¹⁸Another important aspect of the reliability of the DTI quantitative method is the presence of satisfactory interrater and intrarater coefficients of variation that would guarantee the robustness of the method. However, the literature data in this issue are scarce and refer mostly to patients.^19,20 Finally, to the best of our knowledge, there is no study of the possible role of different b-values in the reliability of the conducted DTI measurements.In the present study, we sought to address the aforementioned lack of data in the literature by performing a study of the reproducibility of FA in healthy adults of a wide age range by using region of interest (ROI)-based analysis. Our null hypothesis was that the interrater variability, as well as the variability observed with 2 different b-values and in 2 scanning sessions, would not be statistically significant.     

Low-grade glioma: correlation of short echo time 1H-MR spectroscopy with 23Na MR imaging

BACKGROUND AND PURPOSE: There is considerable variability in the clinical behavior and treatment response of low-grade (WHO grade II) gliomas. The purpose of this work was to characterize the metabolic profile of low-grade gliomas by using short echo time ¹H-MR spectroscopy and to correlate metabolite levels with MR imaging-measured sodium (²³Na) signal intensity. Based on previous studies, we hypothesized decreased N-acetylaspartate (NAA) and increased myo-inositol (mIns), choline (Cho), glutamate (Glu), and ²³Na signal intensity in glioma tissue.MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained for all of the subjects. Proton (¹H-MR) spectroscopy (TR/TE = 2200/46 ms) and sodium (²³Na) MR imaging were performed at 4T in 13 subjects (6 women and 7 men; mean age, 44 years) with suspected low-grade glioma. Absolute metabolite levels were quantified, and relative ²³Na levels were measured in low-grade glioma and compared with the contralateral side in the same patients. Two-sided Student t tests were used to test for statistical significance.RESULTS: Significant decreases were observed for NAA (P < .001) and Glu (P = .004), and increases were observed for mIns (P = .003), Cho (P = .025), and sodium signal intensity (P < .001) in low-grade glioma tissue. Significant correlations (r² > 0.25) were observed between NAA and Glu (P < .05) and between NAA and mIns (P < .01). Significant correlations were also observed between ²³Na signal intensity and NAA (P < .01) and between ²³Na signal intensity and Glu (P < .01). Ratios of NAA/mIns, NAA/²³Na, and NAA/Cho were altered in glioma tissue (P < .001); however based on the t statistic, NAA/²³Na (t = 9.6) was the most significant, followed by NAA/mIns (t = 6.1), and NAA/Cho (t = 5.0).CONCLUSION: Although Glu concentration is reduced and mIns concentration is elevated in low-grade glioma tissue, the NAA/²³Na ratio was the most sensitive indicator of pathologic tissue.

Low-grade (WHO grade II) gliomas, including astrocytoma, oligodendroglioma, and mixed glioma (oligoastrocytoma), account for 10%–20% of primary brain tumors in adults.¹ Although such tumors are more indolent than high-grade gliomas, there is considerable variability in their clinical behavior.² They are capable of malignant transformation and, ultimately, are almost universally fatal. Pathologically, these tumors are diffuse and infiltrative but lack such anaplastic features as necrosis, endothelial proliferation, and mitotic activity.³Tailoring treatment to the individual patient requires a better understanding of the factors that account for the variability in tumor behavior.^{4, 5} Currently, neither the appearance of a low-grade glioma on conventional MR imaging nor tumor pathology can completely predict future tumor behavior or response to treatment. Metabolic profiling of these tumors with MR spectroscopy has the potential to improve our ability to predict the biological behavior and treatment response of low-grade gliomas and to better delineate tumor boundaries. Previous in vitro and in vivo MR spectroscopy studies have identified metabolic markers that help noninvasively discriminate tumor type,^6–8 aid in radiation treatment planning,⁹ or predict survival.¹⁰ Most studies have used long echotime spectroscopy acquisitions (TE ≥ 130 ms), limiting tumor metabolite characterization to the dominant peaks in the ¹H spectrum: N-acetylaspartate (NAA; a putative marker of neuronal viability), total creatine (Cr; involved in energy metabolism), choline-containing compounds (Cho; associated with membrane breakdown/synthesis), and lactate (associated with anaerobic glycolysis). Typically, low-grade glioma is characterized by reduced NAA due to reduced neuronal attenuation, reduced Cr due to a hypermetabolic state, and increased Cho, reflecting increased membrane turnover.^{6, 8} The metabolites glutamate (Glu) and myo-inositol (mIns), measurable by shorter echotime ¹H-MR spectroscopy, may provide additional information about the pathologic state of the neoplasm. A previous study¹¹ has demonstrated that highly malignant tumors may release excess Glu to kill surrounding tissue and promote tumor growth, and increased Glu plus glutamine (Gln) has been measured previously in oligodendroglioma by ¹H-MR spectroscopy.¹² mIns activation of protein kinase C¹³ has also been associated with tumor malignancy. The limited use of short echotime ¹H-MR spectroscopy is due mainly to the difficulty in quantifying metabolites with complicated j-modulated spectral line shapes and the uncertainty introduced by less well-characterized macromolecule resonances beneath the metabolites of interest.Tumors may also be characterized by the local concentration of total sodium, which is sensitive to changes in the tumor microstructure.^14–16 For example, neoplastic cell proliferation and packing, cell death, and necrosis expand the extracellular space in tumors. A defective blood-brain barrier in tumors also permits water, electrolytes, and proteins to enter the extracellular space leading to vasogenic edema. Because both intracellular and extracellular sodium levels may be increased in tumors, ²³Na MR imaging represents a potentially sensitive and noninvasive means of monitoring tissue sodium content related to cancer pathology.^15–18The purpose of this study was to prospectively characterize the metabolic profile of low-grade gliomas by using ¹H-MR spectroscopy and to correlate metabolite levels with MR imaging-measured sodium signal intensity. Based on previous studies, it was hypothesized that levels of NAA would be reduced, and levels of Cho, mIns, Glu, and ²³Na signal intensity would be increased in low-grade glioma compared with normal tissue.     

Prognostic value of perfusion MR imaging of high-grade astrocytomas: long-term follow-up study

BACKGROUND AND PURPOSE: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma.MATERIALS AND METHODS: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23–76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors.RESULTS: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (≤2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163–29.788), maximum rCBV (4.739; 95% CI, 1.950–11.518), extent of surgery (2.692; 95% CI, 1.196–6.061), and sex (2.632; 95% CI, 1.153–6.010).CONCLUSION: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

High-grade astrocytomas (WHO class III or IV) are the most common primary neoplasms of the central nervous system; patients with this disease have a poor prognosis.^1–3 The median survival is approximately 3 years for anaplastic astrocytoma (AA) and 1 year for glioblastoma multiforme (GBM).^1–5 The prognosis of these tumors varies from patient to patient despite identical histopathologic diagnoses; the reasons for this difference are not fully understood.Although histopathologic assessment remains the reference standard for determining the glioma grade, sampling error, large range of WHO classification and grading systems, inter- and intrapathologist variability, and difference in biology within WHO grades of gliomas may result in inadequate evaluation of the entire tumor.^6–9 Thus, for a final brain tumor diagnosis, imaging studies may provide information in addition to the pathologic assessment.Perfusion MR imaging yields physiologic information on in vivo tumor neovascularity and angiogenesis in terms of the relative cerebral blood volume (rCBV).^10–14 Tumor angiogenesis is an important factor that defines the biologic aggressiveness of astrocytomas,¹⁵ and perfusion MR imaging may provide a means for characterizing the vascularity of gliomas, thereby overcoming some of the limitations of histopathologic evaluation. Perfusion MR imaging has been used to grade gliomas, and because higher vascularity corresponds to a higher tumor grade, high-grade gliomas can be expected to manifest high rCBV values.^10–13 Although the prognostic value of perfusion MR imaging in various gliomas has been investigated,^16–20 that in high-grade astrocytomas alone has not been fully evaluated. Our hypothesis was that the rCBV of the tumor seen on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma. The purpose of our study was to verify the hypothesis by using the MR imaging data of our institution and long-term follow-up results.     

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.     

The added value of apparent diffusion coefficient to cerebral blood volume in the preoperative grading of diffuse gliomas

BACKGROUND AND PURPOSE:In cerebral gliomas, rCBV correlates with tumor grade and histologic findings of vascular proliferation. Moreover, ADC assesses water diffusivity and is inversely correlated with tumor grade. In the present work, we have studied whether combined rCBV and ADC values improve the diagnostic accuracy of MR imaging in the preoperative grading of gliomas.MATERIALS AND METHODS:One hundred sixty-two patients with histopathologically confirmed diffuse gliomas underwent DWI and DSC. Mean rCBV and ADC values were compared among the tumor groups with the Student t test or ANOVA. ROC analysis was used to determine rCBV and ADC threshold values for glioma grading.RESULTS:rCBV had significantly different values between grade II and IV gliomas and between grade III and IV tumors, but there were no significant differences between grade II and III gliomas (P > .05). Grade II and III tumors also did not differ when astrocytomas, oligodendrogliomas, and oligoastrocytomas were considered separately. ADC values were significantly different for all 3 grades. The ADC threshold value of 1.185 × 10⁻³ mm²/s and the rCBV cutoff value of 1.74 could be used with high sensitivity in the characterization of high-grade gliomas. The area under the ROC curve for the maximum rCBV and minimum ADC was 0.72 and 0.75, respectively. The combination of rCBV and ADC values increased the area under the ROC curve to 0.83.CONCLUSIONS:ADC measurements are better than rCBV values for distinguishing the grades of gliomas. The combination of minimum ADC and maximum rCBV improves the diagnostic accuracy of glioma grading.

Gliomas are the most common primary neoplasms of the brain in adults,^1,2 ranging in grade from low to high. Glioma grading is based on the histopathologic assessment of the tumor and is critical for planning therapeutic approaches and assessing prognosis and response to therapy.² Advanced MR imaging techniques such as DSC and DWI provide physiologic information that complements the anatomic information obtained from conventional MR imaging.^3–6 DWI quantifies cellularity on the basis of the premise that water diffusivity within the extracellular compartment is inversely related to the content and attenuation of the intracellular space.⁷ The higher the tumor cellularity and grade are, the lower the ADC is because of decreased water diffusivity.^6–8 However, other factors may be complicating this relationship: ADC increases with increased edema and increased edema is seen in high-grade tumors. DSC provides noninvasive assessment of tumor vascularity and angiogenesis^3–6,9 through the examination of the degradation of signal intensity with time associated with the first pass of a bolus of paramagnetic contrast agent.⁹ Because higher vascularity corresponds to a higher tumor grade, as the grade of the astrocytoma increases, the maximum tumor CBV tends to increase.^3,6,7The aim of this study was to evaluate the diagnostic accuracy of combined ADC and CBV values in the preoperative differentiation of diffuse gliomas. Our objectives were the following: 1) to calculate CBV and ADC values for diffuse gliomas included in the study, 2) to establish whether there is any difference in rCBV and ADC values in gliomas classified by tumor grade and histology, 3) to estimate a cutoff CBV and ADC value for differentiation of high- and low-grade gliomas, and 4) to investigate whether combined CBV and ADC values improve the diagnostic accuracy of MR imaging.     

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.     

Analysis of 11C-methionine uptake in low-grade gliomas and correlation with proliferative activity

BACKGROUND AND PURPOSE: The relationship of ¹¹C-methionine (MET) uptake and tumor activity in low-grade gliomas (those meeting the criteria for World Health Organization [WHO] grade II gliomas) remains uncertain. The aim of this study was to compare MET uptake in low-grade gliomas and to analyze whether MET positron-emission tomography (PET) can estimate tumor viability and provide evidence of malignant transformation.MATERIALS AND METHODS: We studied glioma metabolic activity in 49 consecutive patients with newly diagnosed grade II gliomas by using MET PET before surgical resection. On MET PET, we measured tumor/normal brain uptake ratio (T/N ratio) in 21 diffuse astrocytomas (DAs), 12 oligodendrogliomas (ODs), and 16 oligoastrocytomas (OAs). We compared MET T/N ratio among these 3 tumors and investigated possible correlation with proliferative activity, as measured by Mib-1 labeling index (LI).RESULTS: MET T/N ratios of DA, OD, and OA were 2.11 ± 0.87, 3.75 ± 1.43, and 2.76 ± 1.27, respectively. The MET T/N ratio of OD was significantly higher than that of DA (P < .005). In comparison of MET T/N ratios with the Mib-1 LI, a significant correlation was shown in DA (r = 0.63; P < .005) but not in OD and OA.CONCLUSION: MET uptake in DAs may be closely associated with tumor viability, which depends on increased amino acid transport by an activated carrier-mediated system. DAs with lower MET uptake were considered more quiescent lesions, whereas DA with higher MET uptake may act more aggressively.

World Health Organization (WHO) grade II brain tumors, such as diffuse astrocytomas (DAs) and oligodendrogliomas (ODs), are classified by low proliferation rates and the lack of malignant histologic features, such as necrosis and vascular proliferation. However, these tumors frequently recur, even after intervals of more than 10 years, and commonly progress to higher-grade lesions.¹ In most studies, the median survival of grade II glioma is 5 to 10 years with a varying clinical course. The initial treatment of grade II gliomas is usually surgical resection, but many of these tumors diffusely infiltrate into healthy brain tissue, making complete resection difficult. Early radiation therapy after surgery has been shown to prolong the time to progression but not overall survival.² Chemotherapy for ODs is increasingly used as primary treatment³; however, long-term advantages including improvement in quality of life are uncertain. Currently, it is not possible to predict the course of grade II gliomas in individual patients, and thus treatment strategies remain controversial.^4,5It has been shown that positron-emission tomography (PET), a noninvasive imaging technique, is helpful in numerous clinical situations.⁶ A relationship has previously been demonstrated between [¹⁸F] fluorodeoxyglucose (FDG) uptake and glioma grade.^7–10 However, FDG uptake in grade II glioma is infrequently seen. Previous studies also have shown a significant correlation between ¹¹C-methionine (MET) uptake and glioma grade.^10–15 In addition, MET uptake has been correlated with Mib-1 labeling index (LI), proliferating cell nuclear antigen, microvessel attenuation, and survival.^14–18 Mib-1 LI is a good marker to determine proliferative activity and has an important role in determining both malignant neoplasm and a patient''s prognosis. To our knowledge, no study has been published regarding MET uptake and proliferative activity for patients with grade II glioma only. It is generally believed that for most patients with grade II gliomas, the tumor will at some point transform into a more malignant form.¹⁹ We hypothesized that MET uptake correlates significantly with proliferative activity and may thus be a predictor of malignant transformation in low-grade gliomas. We therefore compared MET uptake in DAs, ODs, and oligoastrocytomas (OAs) and investigated correlation with proliferative activity, as measured by Mib-1 LI.     

Incidental acute infarcts identified on diffusion-weighted images: a university hospital-based study

BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood and accumulation of small infarctions may be one of the possible sources of such white matter lesions. Thus, the purpose of this study was to identify the rate of incident infarction as depicted on diffusion-weighted images (DWIs) obtained from a general patient population.MATERIALS AND METHODS: During the 4-year study period, a total of 60 patients (36 men and 24 women) had an incidental DWI-defined infarction without overt clinical symptoms suggestive of a stroke or a transient ischemic attack. All of the MR images were obtained by using a similar protocol on 2 identical 1.5T whole-body scanners. The patient''s vascular risk factors, as well as the presence of white matter lesions (WMLs) on MR imaging and atheromatous changes on MR angiography, were assessed retrospectively. The incidental DWI-defined infarcts were also characterized in terms of their lateralization, lobe, and specific location.RESULTS: A total of 16,206 consecutive brain MR images were done during the study period; the overall incidence of incidental infarcts was 0.37%. Most of these patients with an incidental infarct had vascular risk factors and WMLs on MR images. Most of these patients (80%) had a single lesion on DWI. A total of 88 lesions were identified; most were located in the white matter of the supratentorial brain, primarily in the frontoparietal lobes. There were also lesions involving the brain stem (n = 2). The lesions involving cerebrum were more commonly located in the right side (right to left = 52:34).CONCLUSION: Small, DWI-defined acute brain infarctions can be found incidentally in an asymptomatic population; this finding may account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

White matter lesions depicted on MR imaging have been a center of debate for many years. These white matter rarefactions were originally described on CT and termed “leukoaraiosis” by Hachinski et al.¹ Epidemiologic studies have shown that leukoaraiosis is correlated with age, hypertension (HT), and arteriosclerosis.^2-6 Other reported causative factors include cigarette smoking⁶ and glucose intolerance.⁵ These predisposing factors are also found in patients with lacunar infarcts; thus, it has been proposed that leukoaraiosis and symptomatic lacunar infarcts share a similar underlying vasculopathy, namely, subcortical occlusive small-vessel disease secondary to arteriolosclerosis.^7-9Population studies have noted that leukoaraiosis progresses over a period of years.^6,10 The mechanism by which these lesions increase over time remains unknown. It has also not been determined whether a new white matter lesion (WML) focus grows slowly over a period of months or whether it suddenly appears and evolves rapidly as an acute infarct. Previously proposed mechanisms include both insidious and acute processes.^11-17 For instance, one of the proposed insidious mechanisms is apoptosis induced by chronic ischemia.¹⁴ Microembolic events have been proposed as an acute pathogenetic process.^15,16 Other proposed etiologies, which could be either insidious or acute, include intermittent changes in cerebral perfusion pressure resulting in incomplete infarction¹⁷ and white matter damage by altered blood-brain barrier permeability.^11-13Whatever the mechanism, these lesions will be seen on diffusion-weighted imaging (DWI), if at least some of them occur due to an acute process. Given that DWI has a unique contrast property and a relatively short acquisition time, this imaging technique has been incorporated into many routine brain MR protocols, including, among others, protocols for strokes,^18-21 headaches, seizures, and tumors.^22-24Over the past few years, we have used DWI for our routine brain protocol assuming that incidental infarcts would be identified on DWI performed in a general patient population. Although relatively uncommon given the total number of MR examinations that were done, a number of patients with incidental acute or subacute infarcts were identified. These patients'' clinical and imaging data were retrospectively analyzed to elucidate the significance of our observations.     

Meta-Analysis of Diffusion Metrics for the Prediction of Tumor Grade in Gliomas

BACKGROUND AND PURPOSE:Diffusion tensor metrics are potential in vivo quantitative neuroimaging biomarkers for the characterization of brain tumor subtype. This meta-analysis analyzes the ability of mean diffusivity and fractional anisotropy to distinguish low-grade from high-grade gliomas in the identifiable tumor core and the region of peripheral edema.MATERIALS AND METHODS:A meta-analysis of articles with mean diffusivity and fractional anisotropy data for World Health Organization low-grade (I, II) and high-grade (III, IV) gliomas, between 2000 and 2013, was performed. Pooled data were analyzed by using the odds ratio and mean difference. Receiver operating characteristic analysis was performed for patient-level data.RESULTS:The minimum mean diffusivity of high-grade gliomas was decreased compared with low-grade gliomas. High-grade gliomas had decreased average mean diffusivity values compared with low-grade gliomas in the tumor core and increased average mean diffusivity values in the peripheral region. High-grade gliomas had increased FA values compared with low-grade gliomas in the tumor core, decreased values in the peripheral region, and a decreased fractional anisotropy difference between the tumor core and peripheral region.CONCLUSIONS:The minimum mean diffusivity differs significantly with respect to the World Health Organization grade of gliomas. Statistically significant effects of tumor grade on average mean diffusivity and fractional anisotropy were observed, supporting the concept that high-grade tumors are more destructive and infiltrative than low-grade tumors. Considerable heterogeneity within the literature may be due to systematic factors in addition to underlying lesion heterogeneity.

Diffusion tensor imaging is an MR imaging technique that can quantify diffusion of water in the brain and characterize the structural integrity of white matter tracts.^1–3 Multiple studies have examined the ability of basic diffusion tensor metrics such as mean diffusivity (MD) or the apparent diffusion coefficient and fractional anisotropy (FA) to discriminate the tumor grade of gliomas. Disruption of normal white matter structural integrity by primary glial neoplasms should theoretically reduce fractional anisotropy and increase mean diffusivity.Mean diffusivity is positively correlated with decreased tumor cellular density and increased patient survival, and significant effects are reported in several studies with respect to discriminating tumor grade specifically by using minimum mean diffusivity (minMD).^4–9 In contradistinction, there is no definitive consensus on the ability of fractional anisotropy to assess tumor grade, cellular density, and parenchymal infiltration or to prognosticate patient survival.^7,10–21 We performed a quantitative meta-analysis of the existing literature to determine the statistical consensus of mean diffusivity and fractional anisotropy in distinguishing tumor grade of gliomas, separately examining the identifiable tumor core and region of peripheral signal abnormality.     

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.     

Effects of age and symptom status on silent ischemic lesions after carotid stenting with and without the use of distal filter devices

BACKGROUND AND PURPOSE: The routine use of distal filter devices during carotid angioplasty and stent placement (CAS) is controversial. The aim of this study was to analyze their effects on the incidence of new diffusion-weighted imaging (DWI) lesions as surrogate markers for stroke in important subgroups.materials and METHODS: DWI was performed immediately before and after CAS in 68 patients with and 175 without protection, and patients were further subdivided according to their age or symptom status.RESULTS: The proportion of patients with new ipsilateral DWI lesion(s) was significantly lower after protected versus unprotected CAS (52% versus 68%), as well as in symptomatic patients (56% versus 74%) or those at or younger than 75 years of age (46% versus 67%; all P < .05). Similarly, the total number of lesions was significantly lower after protected versus unprotected CAS (median, 1; interquartile range [IQR], 0–2; versus median, 1; IQR 0–4.75) and in symptomatic patients (median, 1; IQR, 0–3; versus median, 2; IQR, 0–6) or those at or younger than 75 years of age (median, 0; IQR, 0–2; versus median, 1; IQR, 0–4; all P < .05). In contrast, for asymptomatic patients (48% versus 52%; P = .8; median, 0; IQR, 0–2; versus median, 1; IQR, 0–2.5; P = .6) or those older than 75 years of age (73% versus 69%; P = .7; median, 1; IQR, 0–4; versus median, 1.5; IQR, 0–5.75; P = .6), the proportion of patients with new lesion(s) and the total number of these lesions were not significantly different between protected and unprotected CAS.CONCLUSIONS: The use of distal filter devices generally reduces the incidence of new DWI lesions; however, this beneficial effect might not necessarily pertain to older and asymptomatic patients.

Carotid endarterectomy (CEA) is currently the accepted standard of treatment for patients with symptomatic and some selected patients with a severe asymptomatic internal carotid artery stenosis.^1,2 In the past few years, however, carotid angioplasty and stent placement (CAS) has emerged as an alternative endovascular treatment strategy for these disorders. Although initial single-center case series and registries have reported acceptable periprocedural complication rates after CAS even in surgical high-risk patients,^3–6 recent randomized trials directly comparing CAS with CEA have produced conflicting results.^7–9 Compared with surgery, CAS potentially has the major disadvantage of producing more emboli to the brain,¹⁰ which has led to the development and widespread application of cerebral protection devices aimed at preventing the passage of embolic material into the cerebral vasculature. Although the concept of cerebral protection is generally appealing and has been corroborated by a meta-analysis of single-center studies and large registries,^6,11 the use of either balloon occlusion techniques or filter systems increases the duration, the technical complexity, as well as the costs of the intervention and is, thus, no panacea for CAS. Indeed, the periprocedural complication rates were comparable between those patients treated with and without cerebral protection in the recently published stent-protected angioplasty versus carotid endarterectomy in symptomatic patients (SPACE) trial.⁷ Moreover, the 30-day incidence of death and stroke was unacceptably high in the Endarterectomy Versus Angioplasty in Patients with Severe Symptomatic Carotid Stenosis Trial despite the use of cerebral protection devices during CAS.⁸ Although these results partially reflect a lack of experience of the interventional physicians in these trials,¹² it is also conceivable that only certain subgroups of patients actually profit from the use of these devices. In fact, it could be speculated that the potential impact of protection devices on outcome is pronounced in those patients who have been shown to have a high risk of embolic complications during unprotected CAS, such as older patients, and is negligible or even harmful in low-risk patients.^6,13 Because of the relatively small number of clinical events after CAS, it has become a major challenge to identify correlates of clinically silent events to define the role of cerebral protection devices on outcome overall, as well as in important subgroups. The use of diffusion-weighted imaging (DWI) to detect clinically silent emboli during CAS as surrogate markers for stroke could pave the way out of this dilemma.^14–16 In support of this notion, we demonstrated recently an overall positive effect of cerebral protection devices on the number of new DWI lesions after CAS, which were closely related to the clinical outcome.¹⁵ Using this prospective and updated CAS series, the aim of this study was to analyze the effects of cerebral protection devices on the incidence of new DWI lesions in 2 important subgroups, namely, younger and older patients, as well as those with a symptomatic or asymptomatic carotid stenosis.     

Isolated cortical signal increase on MR imaging as a frequent lesion pattern in sporadic Creutzfeldt-Jakob disease

BACKGROUND AND PURPOSE: Hyperintense basal ganglia on MR imaging support the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Our aim was to study the frequency of patients with sporadic CJD presenting with and without characteristic basal ganglia lesions on MR imaging and to examine the corresponding patient characteristics.MATERIALS AND METHODS: Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted images (DWI) of 55 patients with CJD were assessed for signal-intensity increase (FLAIR) or restricted diffusion (DWI) in 7 cortex regions and the basal ganglia, thalamus, and cerebellum. Patient characteristics as well as electroencephalography, CSF, and codon 129 genotype of the prion protein gene (PRNP) were correlated with the most frequent MR imaging lesion patterns.RESULTS: Two major lesion patterns were identified by DWI: cortex and basal ganglia involvement (two thirds) and isolated cortex involvement (one third). In the latter patient group, the cortex involvement was widespread (at least 3 regions affected in 89% on DWI) and usually included the frontal and parietal lobes (78%). The length of the disease course was significantly prolonged (median, 12 versus 5 months). No significant differences were observed concerning electroencephalography and CSF findings and codon 129 genotype distributions. Of 4 patients with normal MR imaging findings, the CSF was positive for the 14-3-3 protein in 3.CONCLUSION: A high number of patients with CJD present without basal ganglia lesions on MR imaging. Isolated cortex involvement on DWI and FLAIR should lead to suggestion of CJD, even if the disease course is only slowly progressive. Additional 14-3-3 protein analysis in the CSF may support the CJD diagnosis.

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare and fatal disease caused by the accumulation of abnormal/pathologic prion protein (PrP^Sc; Sc indicates scrapie) in the human brain. The classic disease type is characterized by rapidly progressive dementia, ataxia, abnormal muscle tone, and myoclonus. It leads to a state of akinetic mutism and death after a median disease duration of 6 months.¹ The definite CJD diagnosis relies on the finding of PrP^Sc in the brain tissue, together with astrocytic gliosis, nerve cell loss, and spongiform degeneration as the typical neuropathologic changes.^2,3During one''s lifetime, MR imaging hyperintensity of the basal ganglia on T2-weighted (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) is increasingly used to support the CJD diagnosis, next to positive CSF (14-3-3 protein) and electroencephalography (EEG) findings of periodic sharp-wave complexes (PSWCs). Although the origin of the signal-intensity changes is still not fully understood, hyperintensity on T2WI and FLAIR has been thought to be caused by gliosis, whereas abnormalities on DWI are most likely derived from spongiform changes.^4–6 DWI was shown to be the most sensitive sequence in the detection of brain lesions, particularly in the neocortex.^7–10 Isolated cortex involvement was also found.^9,11Although abnormal MR imaging findings in CJD have been studied in detail with respect to their location, few attempts have been made to define the most frequently occurring patterns of hyperintensity in a spectrum of patients. Six disease phenotypes (MM1, MM2, MV1, MV2, VV1, and VV2) defined by the codon 129 genotype (MM, MV, VV) of the prion protein gene (PRNP) and pathologic isotype of the PrP^Sc type 1 or 2 have been recently described with distinctive neuropathologic features and various clinical and diagnostic findings.^1–3,12 On MR imaging, predominant cortical (VV1)¹³ or subcortical involvement (MV2 and VV2)^14,15 or no abnormalities (MM2)^16,17 were found in smaller case series.To date, to our knowledge, the overall distribution of MR imaging abnormalities has not been studied in a larger spectrum of patients with CJD, and it is unclear whether there are clinical correlates corresponding to specific MR imaging lesion patterns. The proportion of patients presenting without basal ganglia abnormalities is unknown.We defined the most frequent MR imaging lesion patterns and corresponding clinical characteristics in a CJD patient collective by using highly sensitive MR images, and we considered a possible influence of the codon 129 genotype of the PRNP. We particularly focused on patients lacking basal ganglia abnormalities on MR imaging and suggested criteria that might support the early CJD diagnosis in these patients.     

Diffusion-weighted MR imaging: diagnosing atypical or malignant meningiomas and detecting tumor dedifferentiation

BACKGROUND AND PURPOSE: Atypical and malignant meningiomas are uncommon tumors with aggressive behavior and higher mortality, morbidity, and recurrence compared with benign tumors. We investigated the utility of diffusion-weighted (DW) MR imaging to differentiate atypical/malignant from benign meningiomas and to detect histologic dedifferentiation to higher tumor grade.MATERIALS AND METHODS: We retrospectively compared conventional and DW MR images (b-value 1000 s/mm²) acquired on a 1.5T clinical scanner between 25 atypical/malignant and 23 benign meningiomas. The optimal cutoff for the absolute apparent diffusion coefficient (ADC) and normalized ADC (NADC) ratio to differentiate between the groups was determined by using receiver operating characteristic (ROC) analysis.RESULTS: Irregular tumor margins, peritumoral edema, and adjacent bone destruction occurred significantly more often in atypical/malignant than in benign meningiomas. The mean ADC of atypical/malignant meningiomas (0.66 ± 0.13 × 10⁻³ mm²/s) was significantly lower compared with benign meningiomas (0.88 ± 0.08 × 10⁻³ mm²/s; P < .0001). Mean NADC ratio in the atypical/malignant group (0.91 ± 0.18) was also significantly lower than the benign group (1.28 ± 0.11; P < .0001), without overlap between groups. ROC analysis showed that ADC and NADC thresholds of 0.80 × 10⁻³ mm²/s and 0.99, respectively, had the best accuracy: at the NADC threshold of 0.99, the sensitivity and specificity were 96% and 100%, respectively. Two patients had isointense benign tumors on initial DW MR imaging, and these became hyperintense with the decrease in ADC and NADC below these thresholds when they progressed to atypical and malignant meningiomas on recurrence.CONCLUSIONS: ADC and NADC ratios in atypical/malignant meningiomas are significantly lower than in benign tumors. Decrease in ADC and NADC on follow-up imaging may suggest dedifferentiation to higher tumor grade.

Meningiomas comprise 14%–20% of all intracranial tumors, with a higher incidence of up to 35.2% among Asians and Africans.¹ Although they are generally benign tumors, up to 10% of meningiomas are atypical or malignant, characterized by nuclear disorganization, necrosis, prominent nucleoli, and increased mitoses on histology. Because of their aggressive behavior, atypical/malignant meningiomas are associated with high morbidity and mortality and may invade the adjacent bone and brain parenchyma. They are also more prone to recur in 29%–41% of patients than typical meningiomas, where the recurrence rate is between 7%–20%.² Although typical extra-axial benign meningiomas are easily diagnosed, distinction from more malignant histologic grades by CT or conventional MR imaging is difficult.³ Neuroimaging features, such as heterogeneous appearance, heterogeneous enhancement, marked perilesional edema, irregular cerebral surface, mushrooming on the outer edge of the lesion, and bone destruction, are not unique or reliable for diagnosing atypical/malignant meningiomas.^4–8 A diagnostic method that can differentiate between benign and atypical/ malignant meningiomas would, therefore, be desirable for surgical planning.Diffusion-weighted (DW) MR imaging has been used to study primary brain tumors, including histologic grading of gliomas and response to treatment.^9–16 Only a few studies have evaluated DW MR imaging for grading meningiomas, and although some have found that apparent diffusion coefficient (ADC) of atypical/malignant meningiomas was significantly lower than benign meningiomas,^2,17 others have not duplicated these results.¹⁶ Furthermore, the accuracy and threshold ADC to distinguish between benign and atypical/malignant meningiomas has not been established. There is also a paucity of literature on the DW MR imaging appearance of malignant transformation of benign meningiomas to higher grade tumors. In this study, we compared DW MR imaging between benign and atypical/malignant groups of meningiomas to estimate the cutoff ADC value for optimal tumor grading and describe imaging features of dedifferentiation of benign meningiomas.     

Perfusion Measurement in Brain Gliomas with Intravoxel Incoherent Motion MRI

BACKGROUND AND PURPOSE:Intravoxel incoherent motion MRI has been proposed as an alternative method to measure brain perfusion. Our aim was to evaluate the utility of intravoxel incoherent motion perfusion parameters (the perfusion fraction, the pseudodiffusion coefficient, and the flow-related parameter) to differentiate high- and low-grade brain gliomas.MATERIALS AND METHODS:The intravoxel incoherent motion perfusion parameters were assessed in 21 brain gliomas (16 high-grade, 5 low-grade). Images were acquired by using a Stejskal-Tanner diffusion pulse sequence, with 16 values of b (0–900 s/mm²) in 3 orthogonal directions on 3T systems equipped with 32 multichannel receiver head coils. The intravoxel incoherent motion perfusion parameters were derived by fitting the intravoxel incoherent motion biexponential model. Regions of interest were drawn in regions of maximum intravoxel incoherent motion perfusion fraction and contralateral control regions. Statistical significance was assessed by using the Student t test. In addition, regions of interest were drawn around all whole tumors and were evaluated with the help of histograms.RESULTS:In the regions of maximum perfusion fraction, perfusion fraction was significantly higher in the high-grade group (0.127 ± 0.031) than in the low-grade group (0.084 ± 0.016, P < .001) and in the contralateral control region (0.061 ± 0.011, P < .001). No statistically significant difference was observed for the pseudodiffusion coefficient. The perfusion fraction correlated moderately with dynamic susceptibility contrast relative CBV (r = 0.59). The histograms of the perfusion fraction showed a “heavy-tailed” distribution for high-grade but not low-grade gliomas.CONCLUSIONS:The intravoxel incoherent motion perfusion fraction is helpful for differentiating high- from low-grade brain gliomas.

An estimated 69,720 new cases of primary central nervous system tumors are expected to be diagnosed in the United States in 2013, of which an estimated 24,620 new cases will be malignant (13,630 in males and 10,990 in females).¹ The 5-year relative survival rate following diagnosis of primary malignant CNS tumors, mostly gliomas, is poor, with an average of 33.8%, but it is age-dependent, decreasing monotonically from 73% for 0–19 years of age to 10% for 65–74 years of age (data from 1995–2009).²The assessment of perfusion characteristics of those lesions by using dynamic susceptibility MR imaging has become an important part of the initial evaluation and follow-up because cerebral blood volume has been shown to correlate with the degree of neovascularization³ and increased local perfusion has been shown to correlate with tumor grading⁴ and prognosis.⁵ Histologically, the assessment of microvascularity is important for the grading of a primary brain tumor⁶ because high-grade neoplasms produce a pathologic microvascular network through neoangiogenesis to satisfy a growing need for nutriments and oxygen.Le Bihan et al⁷ have proposed measuring microvascular perfusion with an MR imaging–based method called intravoxel incoherent motion (IVIM) imaging. The incoherent motion of spins, which can be understood as the spatial “mixing” of spins during the time of measurement, reduces exponentially the signal amplitude obtained from a diffusion-weighted sequence such as the Stejskal-Tanner sequence.⁸ This incoherent motion arises inevitably from the thermal diffusion characterized by diffusion coefficient (D) and, in biologic perfused tissue, from movements of blood in the microvasculature, called by analogy pseudodiffusion and characterized by pseudodiffusion coefficient (D*).Therefore, an IVIM biexponential signal equation⁷ has been proposed to model incoherent motion in biologic tissue, with the perfusion fraction (f) describing the fraction of incoherent signal arising from the vascular compartment in each voxel over the total incoherent signal. Furthermore, under the assumption of an isotropic, randomly laid microvascular network, a linear relationship were derived⁹ between D* and fD* (the scalar multiplication of f and D*, referred to as the flow-related parameter) and CBV, MTT⁻¹, and CBF, respectively.Recently, IVIM showed promising results in helping discriminate high- and low-grade tumors, for example in the salivary gland, among Warthin tumors, pleomorphic adenomas, and malignant tumors¹⁰; in the pancreas between healthy pancreas and pancreatic cancer¹¹; or between renal¹² and breast tumor subtypes.¹³ In the brain, where initial reports were made,^7,14–19 IVIM perfusion parameters showed recently a gradual increase in response to gradual increase of hypercapnia.²⁰The purpose of this study was to evaluate the utility of IVIM perfusion parameters (f, D*, and fD*) to differentiate high- and low-grade brain gliomas.