The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma.

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBVmean and rCBVmax), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBVperi-tumor) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBVmax and mTOR based on Pearson's correlations with Benjamini-Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBVperi-tumor showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBVperi-tumor value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBVperi-tumor and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBVperi-tumor has better prognostic value than genomic biomarkers alone.

Advanced MR diffusion tensor imaging and perfusion weighted imaging of intramedullary tumors and tumor like lesions in the cervicomedullary junction region and the cervical spinal cord.

Differential diagnosis between intramedullary tumors and tumor-like lesions (TLL) in the cervicomedullary junction region and cervical spinal cord is important, sometimes clinical dilemma on conventional MR imaging and empirical treatment. We evaluated advanced MR diffusion tensor imaging (DTI) and perfusion weighted imaging (PWI) in 25 patients, including 12 with intramedullary tumors and 13 with TLL in the cervicomedullary junction region and cervical spinal cord. We found that mean fractional anisotropy value of tumors was significantly lower than the value found in TLL, and the mean trace apparent diffusion coefficient and peak height values of tumors were significantly higher (P < 0.05). The receiver operating characteristic curve analysis showed that peak height was better than any of the other imaging parameters, with a sensitivity of 90.9% and specificity of 80% using a cutoff value of 4.523 to differentiate between tumors and TLL. In conclusion, the MR DTI and PWI could be useful in differentiating between intramedullary tumors and TLL in the cervicomedullary junction region and cervical spinal cord.

Correlation between progression free survival and dynamic susceptibility contrast MRI perfusion in WHO grade III glioma subtypes.

The purpose of this study was to determine whether dynamic susceptibility contrast MR perfusion relative cerebral blood volume (rCBV) correlates with prognosis of World Health Organization (WHO) grade III glial tumors and their different subtypes. Retrospective evaluation of pre-treatment tumor rCBV derived from dynamic susceptibility contrast MR perfusion was performed in 34 patients with histopathologically diagnosed WHO grade III glial tumors (anaplastic astrocytomas (n = 20), oligodendrogliomas (n = 4), and oligoastrocytomas (n = 10)). Progression free survival was correlated with rCBV using Spearman rank analysis. ROC curve analysis was performed to determine the operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time. For all grade III tumors (n = 34) the mean rCBV was 2.51 with a progression free survival of 705.5 days. The mean rCBV of anaplastic astrocytomas was 2.47 with progression free survival 495.2 days. In contrast, the mean rCBV for oligodendroglial tumors was 2.56 with a progression free survival of 1005.6 days. Although there was no significant correlation between rCBV and progression free survival among all types of grade III gliomas (P = 0.12), among anaplastic astrocytomas there was a significant correlation between pretreatment rCBV and progression free survival with correlation coefficient of -0.51 (P = 0.02). The operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time (446.5 days) was 2.86 with 78 % accuracy and there was a significant difference between the survival of patients with anaplastic astrocytomas in the dichotomized groups (P = 0.0009). Pre-treatment rCBV may serve as a prognostic imaging biomarker for anaplastic astrocytomas, but not grade III oligodendroglioma tumors.

Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study.

HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤ 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.

Lesions masquerading as acute stroke.

Rapid and accurate recognition of lesions masquerading as acute stroke is important. Any incorrect or delayed diagnosis of stroke mimics will not only increase the risk of being exposed to unnecessary and possibly dangerous interventional therapies, but will also delay proper treatment. In this article, written from a neuroradiologist's perspective, we classified these lesions masquerading as acute stroke into three groups: lesions that may have "normal imaging," lesions that are "symptom mimics" but on imaging clearly not a stroke, and lesions that are "symptom and imaging mimics" with imaging findings similar to stroke. We focused the review on neuroimaging findings of the latter two groups ending with a suggestion for a diagnostic approach in the form of an algorithm.

A representative cohort of patients with non-progressive multiple sclerosis at the age of normal life expectancy.

Multiple sclerosis may have a non-progressive symptomatology for decades; however, it is not clear whether the disease activity may abate completely. We identified a cohort of patients, resident in Gothenburg at the time of disease onset, between the years 1950-64 (n = 307). These geographical and temporal restrictions, along with favourable conditions for a 'spider' epidemiological study, were optimal for an unbiased selection; this 15-year incidence cohort was essentially followed prospectively for 37-59 years after onset. The shortest follow-up time for patients without primary or secondary progression was 45 years. For patients with an initial relapsing-remitting course and multiple sclerosis diagnosis according to the Poser criteria (n = 202), the probability of non-progressive disease after 40 years was 22% (standard error 3.0%), and after 50 years it was 14% (standard error 3.2%). For attack onset including patients with possible multiple sclerosis, the corresponding probabilities after 40 and 50 years were 35% (standard error 3.3%) and 28% (standard error 3.5%), respectively. At the last follow-up in 2009-10, when patients reached the average age of the Swedish population life expectancy, only 13 patients from the multiple sclerosis diagnosis cohort, according to the Poser criteria, remained alive and non-progressive. Their annualized attack frequency diminished with time from 0.29 to 0.015. These patients had been functioning well socially. Nine patients had an Expanded Disability Status Scale score of 0-2.5, and four patients had a score of 3 or 3.5, with deficits dating back to attacks decades ago. Eight patients participated in a complete neuropsychological examination, which showed a slight difference (P < 0.01) concerning verbal memory and executive function compared to an age and socially matched reference group, whereas results for five other cognitive domains were within the normal range. Magnetic resonance images fulfilled the Barkhof-Tintoré criteria for multiple sclerosis in 10 of 11 patients, with conspicuously few subcortical lesions relative to extensive periventricular lesions and lesions extending from the inferior midline aspect of the corpus callosum. Prediction of the non-progressive stage was possible with moderate hazard ratios and low sensitivity. Early features that predicted a non-progressive course were complete remission of the onset attack, low or moderate initial relapse frequency and-when the patients with possible multiple sclerosis were included-dominating afferent symptoms. The clinical disease activity had abated in these 13 patients, with the caveat that transition to secondary progression continued to occur after four decades, albeit with decreasing risk.

Spurious progression in pediatric brain tumors.

In this study, we sought to characterize post-therapy MRI changes mimicking progression, which we refer to as "spurious progression" (SP) in children with brain tumors. We analyzed whether SP is associated with particular tumor types or therapeutic modalities. Between 2000 and 2009, we identified 181 consecutive children <21 years of age at our center who were treated for brain tumors and had at least three MRI scans within a year after completing therapy. SP was defined as MRI abnormalities characterized by increase in size, enhancement, edema, or cystic changes within 12 months following therapy, and stabilization or improvement on subsequent imaging. One-hundred forty-one patients with brain tumors were evaluable. Fifty-six (40%) had imaging abnormalities initially suggestive of disease progression; of these, 34 (24%) had true disease progression (TP). The remaining 22 (16%) had SP based on either stability, decrease in enhancement, edema, size, or disappearance of these cystic or non-cystic abnormalities. SP occurred in patients with low grade (n = 20) and high grade lesions (n = 2). Median time to SP was 2.4 months (range, 0.7-8.3 months), with time to stability, decrease, or disappearance at a median of 4 months (range 1.4-7.7 months). Five patients were clinically symptomatic from SP and were treated with steroids, cyst drainage, and/or surgery. Therefore, SP occurs more commonly in children with low grade tumors, but can also occur with high grade brain tumors, regardless of therapeutic approach.

Diffusion-weighted imaging for differentiating benign from malignant skull lesions and correlation with cell density.

OBJECTIVE: The objective of our study was to determine the utility of diffusion-weighted imaging (DWI) and cell density for differentiating benign from malignant skull lesions. MATERIALS AND METHODS: A retrospective review was performed. Minimum apparent diffusion coefficient (ADC) values were measured and normalized to white matter, which we refer to as "normalized ADC," in 24 skull lesions (12 malignant and 12 benign) in 18 patients. In addition, cell densities were measured in 15 cases and correlated with ADC values. RESULTS: The average minimum ADC in malignant tumors was 0.70 × 10(-3) mm(2)/s versus 1.11 × 10(-3) mm(2)/s in benign tumors (p = 0.0037). Similarly, the average normalized ADC for malignant tumors was 1.03, whereas the average normalized ADC for benign tumors was 1.65 (p = 0.0012). Receiver operating characteristic curve analysis yielded optimal normalized ADC and ADC thresholds of 1.23 (accuracy, 84.6%; sensitivity, 75.0%; specificity, 92.3%) and 1.01 × 10(-3) mm(2)/s (accuracy, 83.7%; sensitivity, 83.3%; specificity, 84.6%), respectively. There was a significant inverse correlation between cell density and normalized ADC (r = -0.58; p = 0.023). The low cellularity in chordoma and low-grade chondrosarcoma and high cellularity in eosinophilic granuloma may explain the DWI features of these lesions. CONCLUSION: ADC values in skull lesions correlate with cell density and can potentially narrow the differential diagnoses for indeterminate skull lesions. Understanding the histopathologic features of skull lesions can refine interpretation of DWI.

Progressive decline in fractional anisotropy on serial DTI examinations of the corpus callosum: a putative marker of disease activity and progression in SPMS.

INTRODUCTION: Clinical trials of secondary progressive multiple sclerosis (SPMS) is lacking reliable biomarkers or outcome measures that reflect tissue injury incurred within a 1- to 2-year observation period. Diffusion tensor imaging (DTI) is sensitive in detecting acute brain tissue damage. We monitored SPMS patients over 12 months for diffusion changes within the corpus callosum (CC). METHODS: Bimonthly MRI examinations over a 1-year period were performed on 11 SPMS patients. The protocol included postcontrast T1-weighted images and DTI. Based on the appearance of T1 enhancing lesion(s) during the study period, the patients were divided into enhancing (five patients) and nonenhancing (six patients) groups. Fractional anisotropy (FA) and mean diffusivity (MD) of the genu, body, and splenium of the CC were measured and temporal changes in mean FA and MD were evaluated for each group as well as between groups. Immunology data from peripheral blood mononuclear cells were also collected on a monthly basis. RESULTS: The enhancing group showed significant, progressive decrease in FA in body (p = 0.012) and splenium (p = 0.033) of CC, and significantly higher lymphotoxin-ß levels. No significant FA changes were seen in the nonenhancing group. Moreover, the FA decline in the enhancing group deviated significantly from the nonenhancing group, which remained essentially stable. Although MD increased slightly in both groups, there was no significant difference between the two groups. CONCLUSION: Based on the MR and immunology findings, the results of our study suggest that DTI undergo more rapid and longitudinal changes in SPMS patients with inflammatory activity.

31P MR spectroscopy to evaluate the efficacy of hepatic artery embolization in the treatment of neuroendocrine liver metastases.

BACKGROUND: It is common to treat patients with metastatic disease from gastrointestinal neuroendocrine (NE) tumors with surgical reduction to prolong survival. This can be combined with hepatic arterial embolization (HAE) and medical treatment to reduce hormonal symptoms. Today there are no rapid and reliable methods to evaluate the efficacy of HAE in the treatment of neuroendocrine liver metastasis. PURPOSE: To investigate metabolic changes in hepatic metastases of NE tumors following HAE, and to establish if there are any early spectral patterns that might indicate therapeutic efficacy based on in vivo (31)P MRS data. MATERIAL AND METHODS: Volume selective (31)P MRS was used to study 11 patients with disseminated NE tumors with regional lymph nodes and bilobar liver metastases. Measurements were performed before and 1 and 3 days after HAE. RESULTS: Non-responders had significantly higher PME/Pi and αNTP/ΣNTP ratios than the responders before HAE (P < 0.05). Three days after HAE, non-responders still had significantly higher αNTP/ΣNTP than the responders did (P < 0.05). We also observed trends for increased PME ratios 3 days after HAE, decreased ATP-levels, and liberated Pi in responders. CONCLUSION: This (31)P-MRS study showed significant differences in PME/Pi and αNTP/ΣP ratios between responders and non-responders on the day before HAE, which is an interesting finding that may reflect intrinsic properties of the tumor tissue. We also observed trends for cell membrane renewal and increased energy consumption in responders after HAE. These results demonstrate potentials for (31)P-MRS to predict individual responsiveness prior to HAE.

Quantification of accuracy and precision of multi-center DTI measurements: a diffusion phantom and human brain study.

The inter-site and intra-site variability of system performance of MRI scanners (due to site-dependent and time-variant variations) can have significant adverse effects on the integration of multi-center DTI data. Measurement errors in accuracy and precision of each acquisition determine both the inter-site and intra-site variability. In this study, multiple scans of an identical isotropic diffusion phantom and of the brain of a traveling human volunteer were acquired at MRI scanners from the same vendor and with similar configurations at three sites. We assessed the feasibility of multi-center DTI studies by direct quantification of accuracy and precision of each dataset. Accuracy was quantified via comparison to carefully constructed gold standard datasets while precision (the within-scan variability) was estimated by wild bootstrap analysis. The results from both the phantom and human data suggest that the inter-site variation in system performance, although relatively small among scanners of the same vendor, significantly affects DTI measurement accuracy and precision and therefore the effectiveness for the integration of multi-center DTI measurements. Our results also highlight the value of a DTI-specific phantom in identifying and quantifying measurement errors due to site-dependent variations in the system performance, and its usefulness for quality assurance/quality control in multi-center DTI studies. In addition, we observed that the within-scan variability of each data acquisition, as assessed by wild bootstrap analysis, is of the same magnitude as the inter-site and intra-site variability. We propose that by weighing datasets based on their variability, as evaluated by wild bootstrap analysis, one can improve the quality of the dataset. This approach will provide a more effective integration of datasets from multi-center DTI studies.

MR perfusion-weighted imaging may help in differentiating between nonenhancing gliomas and nonneoplastic lesions in the cervicomedullary junction.

PURPOSE: To evaluate the ability of dynamic susceptibility-weighted contrast-enhanced magnetic resonance (MR) perfusion imaging (DSC-PWI) in distinguishing between nonenhancing gliomas and nonenhancing, nonneoplastic lesions in the cervicomedullary junction region. MATERIALS AND METHODS: This retrospective study involved eight patients with nonenhancing gliomas in the medulla oblongata and eight patients with nonenhancing nonneoplastic lesions. The relative cerebral blood volume (rCBV) ratios, peak heights, and percentage of signal intensity recovery derived from time-signal intensity curves of these nonenhancing lesions were compared. RESULTS: The mean peak height of nonenhancing gliomas was significantly higher than the value of their reference regions of interest (ROIs). In contrast, mean peak height of nonneoplastic lesions was significantly lower than their reference ROIs. The mean peak height and mean maximal rCBV ratio of nonenhancing gliomas were significantly higher than those of nonenhancing, nonneoplastic lesions (P<0.05). There was no significant difference with regard to percentage of signal intensity recovery between the two groups. CONCLUSION: DSC-PWI could be a useful adjuvant tool to differentiate between nonenhancing gliomas and nonenhancing, nonneoplastic lesions in the cervicomedullary junction region.

Border zone infarcts: pathophysiologic and imaging characteristics.

Border zone or watershed infarcts are ischemic lesions that occur in characteristic locations at the junction between two main arterial territories. These lesions constitute approximately 10% of all brain infarcts and are well described in the literature. Their pathophysiology has not yet been fully elucidated, but a commonly accepted hypothesis holds that decreased perfusion in the distal regions of the vascular territories leaves them vulnerable to infarction. Two types of border zone infarcts are recognized: external (cortical) and internal (subcortical). To select the most appropriate methods for managing these infarcts, it is important to understand the underlying causal mechanisms. Internal border zone infarcts are caused mainly by hemodynamic compromise, whereas external border zone infarcts are believed to result from embolism but not always with associated hypoperfusion. Various imaging modalities have been used to determine the presence and extent of hemodynamic compromise or misery perfusion in association with border zone infarcts, and some findings (eg, multiple small internal infarcts) have proved to be independent predictors of subsequent ischemic stroke. A combination of several advanced techniques (eg, diffusion and perfusion magnetic resonance imaging and computed tomography, positron emission tomography, transcranial Doppler ultrasonography) can be useful for identifying the pathophysiologic process, making an early clinical diagnosis, guiding management, and predicting the outcome.

Changes in relative cerebral blood volume 1 month after radiation-temozolomide therapy can help predict overall survival in patients with glioblastoma.

PURPOSE: To evaluate perfusion parameter changes in patients with glioblastoma multiforme by comparing the perfusion magnetic resonance (MR) imaging measurements obtained before combined radiation and temozolomide therapy (RT-TMZ) with the follow-up MR imaging measurements obtained 1 month after completion of this treatment. MATERIALS AND METHODS: Institutional review board approval was obtained, and HIPAA guidelines were followed. The data of 36 patients (24 male [median age, 63 years]; 12 female [median age, 59 years]) with glioblastoma multiforme who were treated with RT-TMZ were retrospectively reviewed. The hypothesis was that a change in relative cerebral blood volume (rCBV) 1 month after RT-TMZ is predictive of overall survival. Linear regression analysis was performed to correlate changes in tumor size and perfusion parameters with overall survival. Receiver operating characteristic (ROC) curves were evaluated for 1-year survival. Overall survival was assessed with Kaplan-Meir survival curves and log-rank testing. RESULTS: Percentage change in rCBV at 1 month after RT-TMZ correlated with overall survival. Increased rCBV after treatment was a strong predictor of poor survival (median survival, 235 days versus 529 days with decreased rCBV) (P < .008, log-rank test). The ROC curves for 1-year survival showed a greater area under the curve (0.806; 95% confidence interval [CI]: 0.698, 0.970) (P = .005) with rCBV than with tumor size (0.556; 95% CI: 0.342, 0.729) (P = .382). The overall survival for patients with increased tumor size, based on Macdonald criteria, was shorter than that for patients who showed no progression (stable or partial response), but the difference was not significant (median survival, 442 days versus 598 days) (P = .761, log-rank test). CONCLUSION: Change in rCBV after RT-TMZ appears to correlate with overall survival.

Anterior to posterior hippocampal MRS metabolite difference is mainly a partial volume effect.

BACKGROUND: The concentration of N-acetylaspartate (NAA) in hippocampus, as measured with magnetic resonance spectroscopy (MRS), and the ratio of NAA/(choline (Cho) + creatine (Cr)) are valuable tools in the lateralization of temporal lobe epilepsy (TLE). MRS of hippocampus is also increasingly used to study certain psychiatric and degenerative diseases. However, the reliability of such measurements of hippocampus has been questioned. PURPOSE: To re-evaluate MRS imaging data from prior control subjects with regard to variation of metabolite concentrations in hippocampus from anterior to posterior and the partial volume (R)contribution to the measurements from adjacent tissue. MATERIAL AND METHODS: Twelve healthy subjects, mean age 33 years, were studied with MRS imaging. The measurement volume was angled along the temporal horns and metabolite concentration images were reconstructed at the MR system. Regions of interest (ROIs) in the anterior, medial, and posterior parts of both hippocampi were evaluated. Signal normalization to the total MRS signal from all ROIs permitted pooling of individual data with different and unknown signal scaling. One subject was re-examined with a high resolution three-dimensional (3D) volume of the brain for evaluation of partial volumes in the MRS examination. RESULTS: Overall, there were significantly lower concentrations of NAA in the anterior parts, and of (Cho+Cr) in the posterior parts, while the NAA/(Cho+Cr) ratio in the posterior parts of the mesial temporal lobes was significantly higher. Hippocampus accounted for one-half, one-third, and one-quarter of the anterior, middle, and posterior ROIs, respectively. The NAA/(Cho+Cr) ratio thus showed a reverse relationship to the relative volume of hippocampal tissue within the ROI. CONCLUSION: Metabolite concentrations in the mesial temporal lobe obtained with MRS imaging represent the mean value of hippocampus and a considerable amount of adjacent tissue. To assess the hippocampus alone, an actual voxel well below 1 cm(3) and a sub-centimeter slice thickness are required.

The correlation of fractional anisotropy parameters with Ki-67 index, and the clinical implication in grading of non-enhancing gliomas and neuronal-glial tumors.

PURPOSE: To investigate the correlation between the FA parameters and Ki-67 labeling index, and their diagnostic performance in grading supratentorial non-enhancing gliomas and neuronal-glial tumors (GNGT). METHODS: This institutional review board-approved, Health Insurance Portability and Accountability (HIPAA) compliant retrospective study enrolled 35 patients, including 19 with low grade GNGT and 16 with high grade GNGT. The mean FA, maximal FA and mean maximal FA values derived from diffusion tensor imaging were measured. The correlation between the FA parameters and the Ki-67 labeling index was assessed by Spearman rank test. The receiver operating characteristic curve analysis and multivariate logistic regression analysis were performed to detect the optimal imaging parameters in grading GNGT. RESULTS: The three FA parameters of low grade GNGT were significantly lower than the high grade GNGT (p < 0.001). The mean FA, maximal FA and mean maximal FA had significant positive correlation with Ki-67 labeling index (p = 0.001, p < 0.001, p < 0.001 respectively). The maximal FA showed a higher sensitivity and specificity in grading of non-enhancing GNGT with specificity of 78.9%, sensitivity of 100.0%, respectively. CONCLUSIONS: The FA parameters correlated with Ki-67 labeling index, and were useful surrogates in preoperative grading supratentorial non-enhancing GNGT.

Accurate and sensitive measurements of magnetic susceptibility using echo planar imaging.

Susceptibility differences are common causes for artifacts in magnetic resonance (MR); therefore, it is important to choose phantom materials in a way that these artifacts are kept at a minimum. In this study, a previously proposed MR imaging (MRI) method [Beuf O, Briguet A, Lissac M, Davis R. Magnetic resonance imaging for the determination of magnetic susceptibility of materials. J Magn Reson 1996; Series B(112):111-118] was improved to facilitate sensitive in-house measurements of different phantom materials so that such artifacts can more easily be minimized. Using standard MRI protocols and distilled water as reference, we measured magnetic volume susceptibility differences with a clinical MR system. Two imaging techniques, echo planar imaging (EPI) and spin echo, were compared using liquid samples whose susceptibilities were verified by MR spectroscopy. The EPI sequence has a very narrow bandwidth in the phase-encoding direction, which gives an increased sensitivity to magnetic field inhomogeneities. All MRI measurements were evaluated in two ways: (1) manual image analysis and (2) model fitting. The narrow bandwidth of the EPI made it possible to detect very small susceptibility differences (equivalent susceptibility difference, Deltachi(e)> or =0.02 ppm), and even plastics could be measured. Model fitting yielded high accuracy and high sensitivity and was less sensitive to other image artifacts as compared with manual image analysis.

Fractional anisotropy is higher in Heschl's gyrus than in superior temporal gyrus in normal subjects.

RATIONALE AND OBJECTIVES: The first Heschl's gyrus (HG) is believed to receive the core projection of the acoustic radiation. We examined if it were possible to differentiate the subcortical white matter of the HG from the superior temporal gyrus (STG) using diffusion tensor (DT) imaging. MATERIALS AND METHODS: The study was approved and informed consent was obtained in accordance with the guidelines of our Institutional Review Board for human subject studies. We examined six healthy adult volunteers with DT images using 20 orientations and repeated 11 times. The fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were calculated. RESULTS: The mean FA of the subcortical white matter of the HG (0.37) was higher than that of the STG (0.27) on both sides (P < .01). There was no statistically significant difference when comparing left and right HG and STG (P > .05). There was no statistically significant difference in mean ADC of the HGs and STGs (0.75 x 10(-3) mm(2)/sec, P > .05). CONCLUSIONS: The FA in the subcortical white matter of the HG was higher than that of the STG in both hemispheres. These changes in DT imaging may be accounted for by the presence of the auditory radiations.

Spatial regression analysis of serial DTI for subject-specific longitudinal changes of neurodegenerative disease.

Quantitative measurement of localized longitudinal changes in brain abnormalities at an individual level may offer critical information for disease diagnosis and treatment. The voxel-wise permutation-based method SPREAD/iSPREAD, which combines resampling and spatial regression of neighboring voxels, provides an effective and robust method for detecting subject-specific longitudinal changes within the whole brain, especially for longitudinal studies with a limited number of scans. As an extension of SPREAD/iSPREAD, we present a general method that facilitates analysis of serial Diffusion Tensor Imaging (DTI) measurements (with more than two time points) for testing localized changes in longitudinal studies. Two types of voxel-level test statistics (model-free test statistics, which measure intra-subject variability across time, and test statistics based on general linear model that incorporate specific lesion evolution models) were estimated and tested against the null hypothesis among groups of DTI data across time. The implementation and utility of the proposed statistical method were demonstrated by both Monte Carlo simulations and applications on clinical DTI data from human brain in vivo. By a design of test statistics based on the disease progression model, it was possible to apportion the true significant voxels attributed to the disease progression and those caused by underlying anatomical differences that cannot be explained by the model, which led to improvement in false positive (FP) control in the results. Extension of the proposed method to include other diseases or drug effect models, as well as the feasibility of global statistics, was discussed. The proposed statistical method can be extended to a broad spectrum of longitudinal studies with carefully designed test statistics, which helps to detect localized changes at the individual level.

Improved spatial regression analysis of diffusion tensor imaging for lesion detection during longitudinal progression of multiple sclerosis in individual subjects.

Subject-specific longitudinal DTI study is vital for investigation of pathological changes of lesions and disease evolution. Spatial Regression Analysis of Diffusion tensor imaging (SPREAD) is a non-parametric permutation-based statistical framework that combines spatial regression and resampling techniques to achieve effective detection of localized longitudinal diffusion changes within the whole brain at individual level without a priori hypotheses. However, boundary blurring and dislocation limit its sensitivity, especially towards detecting lesions of irregular shapes. In the present study, we propose an improved SPREAD (dubbed improved SPREAD, or iSPREAD) method by incorporating a three-dimensional (3D) nonlinear anisotropic diffusion filtering method, which provides edge-preserving image smoothing through a nonlinear scale space approach. The statistical inference based on iSPREAD was evaluated and compared with the original SPREAD method using both simulated and in vivo human brain data. Results demonstrated that the sensitivity and accuracy of the SPREAD method has been improved substantially by adapting nonlinear anisotropic filtering. iSPREAD identifies subject-specific longitudinal changes in the brain with improved sensitivity, accuracy, and enhanced statistical power, especially when the spatial correlation is heterogeneous among neighboring image pixels in DTI.