Longitudinal Evaluation of DCE-MRI as an Early Indicator of Progression after Standard Therapy in Glioblastoma.

Background and Purpose: Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI. Methods: We identified 26 patients from 2011 to 2023 with newly diagnosed primary glioblastoma by histopathology and gross or subtotal resection of the tumor. Then, we classified them into two groups: patients with progression of disease (POD) confirmed by pathology or change in chemotherapy and patients with stable disease without evidence of progression or need for therapy change. Finally, at least three DCE-MRI scans were performed prior to POD for the progression cohort, and three consecutive DCE-MRI scans were performed for those with stable disease. The volume of interest (VOI) was delineated by a neuroradiologist to measure the maximum values for Ktrans and plasma volume (Vp). A Friedman test was conducted to evaluate the statistical significance of the parameter changes between scans. Results: The mean interval between subsequent scans was 57.94 days, with POD-1 representing the first scan prior to POD and POD-3 representing the third scan. The normalized maximum Vp values for POD-3, POD-2, and POD-1 are 1.40, 1.86, and 3.24, respectively (FS = 18.00, p = 0.0001). It demonstrates that Vp max values are progressively increasing in the three scans prior to POD when measured by routine MRI scans. The normalized maximum Ktrans values for POD-1, POD-2, and POD-3 are 0.51, 0.09, and 0.51, respectively (FS = 1.13, p < 0.57). Conclusions: Our analysis of the longitudinal scans leading up to POD significantly correlated with increasing plasma volume (Vp). A longitudinal study for tumor perfusion change demonstrated that DCE perfusion could be utilized as an early predictor of tumor progression.

Delay of Aortic Arterial Input Function Time Improves Detection of Malignant Vertebral Body Lesions on Dynamic Contrast-Enhanced MRI Perfusion.

Dynamic contrast-enhanced MRI (DCE) is an emerging modality in the study of vertebral body malignancies. DCE-MRI analysis relies on a pharmacokinetic model, which assumes that contrast uptake is simultaneous in the feeding of arteries and tissues of interest. While true in the highly vascularized brain, the perfusion of the spine is delayed. This delay of contrast reaching vertebral body lesions can affect DCE-MRI analyses, leading to misdiagnosis for the presence of active malignancy in the bone marrow. To overcome the limitation of delayed contrast arrival to vertebral body lesions, we shifted the arterial input function (AIF) curve over a series of phases and recalculated the plasma volume values (Vp) for each phase shift. We hypothesized that shifting the AIF tracer curve would better reflect actual contrast perfusion, thereby improving the accuracy of Vp maps in metastases. We evaluated 18 biopsy-proven vertebral body metastases in which standard DCE-MRI analysis failed to demonstrate the expected increase in Vp. We manually delayed the AIF curve for multiple phases, defined as the scan-specific phase temporal resolution, and analyzed DCE-MRI parameters with the new AIF curves. All patients were found to require at least one phase-shift delay in the calculated AIF to better visualize metastatic spinal lesions and improve quantitation of Vp. Average normalized Vp values were 1.78 ± 1.88 for zero phase shifts (P0), 4.72 ± 4.31 for one phase shift (P1), and 5.59 ± 4.41 for two phase shifts (P2). Mann-Whitney U tests obtained p-values = 0.003 between P0 and P1, and 0.0004 between P0 and P2. This study demonstrates that image processing analysis for DCE-MRI in patients with spinal metastases requires a careful review of signal intensity curve, as well as a possible adjustment of the phase of aortic AIF to increase the accuracy of Vp.

Semisupervised Training of a Brain MRI Tumor Detection Model Using Mined Annotations.

Background Artificial intelligence (AI) applications for cancer imaging conceptually begin with automated tumor detection, which can provide the foundation for downstream AI tasks. However, supervised training requires many image annotations, and performing dedicated post hoc image labeling is burdensome and costly. Purpose To investigate whether clinically generated image annotations can be data mined from the picture archiving and communication system (PACS), automatically curated, and used for semisupervised training of a brain MRI tumor detection model. Materials and Methods In this retrospective study, the cancer center PACS was mined for brain MRI scans acquired between January 2012 and December 2017 and included all annotated axial T1 postcontrast images. Line annotations were converted to boxes, excluding boxes shorter than 1 cm or longer than 7 cm. The resulting boxes were used for supervised training of object detection models using RetinaNet and Mask region-based convolutional neural network (R-CNN) architectures. The best-performing model trained from the mined data set was used to detect unannotated tumors on training images themselves (self-labeling), automatically correcting many of the missing labels. After self-labeling, new models were trained using this expanded data set. Models were scored for precision, recall, and F1 using a held-out test data set comprising 754 manually labeled images from 100 patients (403 intra-axial and 56 extra-axial enhancing tumors). Model F1 scores were compared using bootstrap resampling. Results The PACS query extracted 31 150 line annotations, yielding 11 880 boxes that met inclusion criteria. This mined data set was used to train models, yielding F1 scores of 0.886 for RetinaNet and 0.908 for Mask R-CNN. Self-labeling added 18 562 training boxes, improving model F1 scores to 0.935 (P < .001) and 0.954 (P < .001), respectively. Conclusion The application of semisupervised learning to mined image annotations significantly improved tumor detection performance, achieving an excellent F1 score of 0.954. This development pipeline can be extended for other imaging modalities, repurposing unused data silos to potentially enable automated tumor detection across radiologic modalities. © RSNA, 2022 Online supplemental material is available for this article.

CNS Metastases in Patients With MET Exon 14-Altered Lung Cancers and Outcomes With Crizotinib.

PURPOSE: Although MET exon 14 (METex14)-altered lung cancers were first identified more than a decade and a half ago, the frequency of CNS metastatic disease remains poorly defined. Furthermore, the seminal trial of crizotinib in these patients (PROFILE 1001) did not report patterns of CNS response or progression. PATIENTS AND METHODS: Patients with pathologically confirmed, advanced non-small-cell lung cancers (NSCLC) harboring a METex14 alteration by targeted DNA/RNA sequencing were studied. The incidence of brain metastases and the outcomes of MET inhibition with crizotinib were analyzed. RESULTS: Eighty-three patients with METex14-altered metastatic NSCLC were identified. The incidence of CNS metastases at diagnosis was 17% (95% CI, 10% to 27%). The lifetime incidence was 36% (95% CI, 26% to 47%); 83% of patients had parenchymal disease, and 17% had leptomeningeal disease. The probability of having brain metastasis at 1, 2, and 3 years was 24%, 35%, and 38%, respectively. Fifty-four patients received crizotinib. The median time to radiologic CNS progression was 5.8 months (range, 3.7-20.0 months). Patterns of crizotinib progression were as follows: intracranial only in 10% of patients, intracranial and extracranial in 12%, and extracranial only in 78%. In patients with brain metastases before treatment, the median time on crizotinib was 7.5 months (range, 7.2-11.7 months). CONCLUSION: CNS metastases, including leptomeningeal disease, occurred in more than a third of patients with METex14-altered lung cancers. In crizotinib-treated patients with or without CNS metastases, CNS failure was seen in less than a quarter of patients on progression.

T1-weighted Dynamic Contrast-enhanced MRI to Differentiate Nonneoplastic and Malignant Vertebral Body Lesions in the Spine.

Background Dynamic contrast agent-enhanced (DCE) perfusion MRI may help differentiate between nonneoplastic and malignant lesions in the spine. Purpose To investigate the correlation between fractional plasma volume (Vp), a parameter derived from DCE perfusion MRI, and histopathologic diagnosis for spinal lesions. Materials and Methods In this retrospective study, patients who underwent DCE perfusion MRI and lesion biopsy between May 2015 and May 2018 were included. Inclusion criteria were short time interval (<30 days) between DCE perfusion MRI and biopsy, DCE perfusion MRI performed before biopsy, and DCE perfusion MRI performed at the same spine level as biopsy. Exclusion criteria were prior radiation treatment on vertebrae of interest, poor DCE perfusion MRI quality, nondiagnostic biopsy, and extensive spinal metastasis or prior kyphoplasty. One hundred thirty-four lesions were separated into a nonneoplastic group (n = 51) and a malignant group (n = 83) on the basis of histopathologic analysis. Two investigators manually defined regions of interest in the vertebrae. DCE perfusion MRI parameter Vp was calculated by using the Tofts pharmacokinetic two-compartment model. Vp was quantified, normalized to adjacent normal vertebrae, and compared between the two groups. A Mann-Whitney U test and receiver operating characteristic analysis was performed to verify the difference in Vp between the nonneoplastic and malignant groups. Reproducibility was assessed by calculating the Cohen κ coefficient. Results One hundred patients (mean age, 65 years ± 11 [standard deviation]; 52 men) were evaluated. Vp was lower in nonneoplastic lesions versus malignant lesions (1.6 ± 1.3 vs 4.2 ± 3.0, respectively; P < .001). The sensitivity of Vp was 93% (77 of 83; 95% confidence interval [CI]: 85%, 97%), specificity was 78% (40 of 51; 95% CI: 65%, 89%), and area under the receiver operating characteristic curve was 0.88 (95% CI: 0.82, 0.95). Cohen κ coefficient suggested substantial agreement in both intra- (κ = 0.72) and interreader (κ = 0.70) reproducibility. Conclusion This study indicated that dynamic contrast agent-enhanced perfusion MRI parameter, fractional plasma volume, was able to differentiate between nonneoplastic spinal lesions and malignant lesions. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Haller in this issue.

Genetic variants and cognitive functions in patients with brain tumors.

BACKGROUND: Patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer's disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population. METHODS: One hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood-brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs. RESULTS: Multivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities. CONCLUSION: This novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

Corticosteroid therapy and severity of vasogenic edema in posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a variable cerebrovascular syndrome associated with hypertension and autoregulatory failure. Steroids have been reported to both precipitate and treat PRES. We sought to determine the prevalence of steroid therapy at the time of PRES and to assess the relationship between steroid therapy and extent of vasogenic edema. METHODS: We performed a retrospective review of radiology reports between 2008 and 2014 from two academic medical centers to identify cases of PRES. Clinical and radiographic data were collected. Descriptive statistics were used to determine the prevalence of corticosteroid therapy at the time of PRES onset and the latency from steroid initiation to PRES onset. The association between steroid therapy and extent of vasogenic edema was assessed in multiple regression models. RESULTS: We identified 99 cases of PRES in 96 patients. The median age was 55years (IQR 30-65) and 74% were women. Steroid therapy at time of PRES onset was identified in 44 of 99 cases. Excluding patients on chronic therapy, the median duration of steroid exposure before PRES onset was 6 (IQR, 3-10) days. Steroid therapy was not associated with extent of vasogenic edema in unadjusted or linear and logistic regression models adjusted for age, sex, and maximum systolic blood pressure on day of onset. CONCLUSION: Corticosteroid therapy, often of brief duration, frequently preceded the onset of PRES and was not associated with severity of vasogenic edema.

Imaging characteristics associated with clinical outcomes in posterior reversible encephalopathy syndrome.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is a disorder of cerebrovascular autoregulation that can result in brain edema, hemorrhage, and infarction. We sought to investigate whether certain imaging characteristics in PRES are associated with clinically significant patient outcomes. METHODS: We retrospectively reviewed all cases of PRES occurring between 2008 and 2014 at two major academic medical centers. Demographic, clinical, and radiographic data were collected. We analyzed imaging studies for vasogenic edema, hemorrhage, and diffusion restriction. We performed univariate analysis and stepwise logistic regression to assess the association between our radiologic findings of interest and clinical outcomes as defined by hospital discharge disposition and modified Rankin scale (mRS) at time of discharge. RESULTS: We identified 99 cases of PRES in 96 patients. The median age was 55 years (IQR 30-65) and 74% were women. In 99 cases, 60% of patients had active cancer, 19% had history of bone marrow or organ transplantation, 14% had autoimmune disease, and 8% were peripartum. Imaging at clinical presentation showed extensive vasogenic edema in 39%, hemorrhage in 36%, hemorrhage with mass effect in 7%, and restricted diffusion in 16%. In our final logistic regression models, the presence of extensive vasogenic edema, hemorrhage with mass effect, or diffusion restriction was associated with worse clinical outcome as defined by both discharge disposition (OR = 4.3; 95% CI: 1.4-36.3; p = 0.047) and mRS (OR = 3.6; 95% CI: 1.2-10.7; p = 0.019). CONCLUSIONS: Extensive vasogenic edema, hemorrhage, and restricted diffusion on initial imaging in PRES are associated with worse clinical outcomes.

Comparison of compressed sensing diffusion spectrum imaging and diffusion tensor imaging in patients with intracranial masses.

PURPOSE: To compare compressed diffusion spectrum imaging (CS-DSI) with diffusion tensor imaging (DTI) in patients with intracranial masses. We hypothesized that CS-DSI would provide superior visualization of the motor and language tracts. MATERIALS AND METHODS: We retrospectively analyzed 25 consecutive patients with intracranial masses who underwent DTI and CS-DSI for preoperative planning. Directionally-encoded anisotropy maps, and streamline hand corticospinal motor tracts and arcuate fasciculus language tracts were graded according to a 3-point scale. Tract counts, anisotropy, and lengths were also calculated. Comparisons were made using exact marginal homogeneity, McNemar's and Wilcoxon signed-rank tests. RESULTS: Readers preferred the CS-DSI over DTI anisotropy maps in 92% of the cases, and the CS-DSI over DTI tracts in 84%. The motor tracts were graded as excellent in 80% of cases for CS-DSI versus 52% for DTI; 58% of the motor tracts graded as acceptable in DTI were graded as excellent in CS-DSI (p=0.02). The language tracts were graded as excellent in 68% for CS-DSI versus none for DTI; 78% of the language tracts graded as acceptable by DTI were graded as excellent by CS-DSI (p<0.001). CS-DSI demonstrated smaller normalized mean differences than DTI for motor tract counts, anisotropy and language tract counts (p≤0.01). CONCLUSION: CS-DSI was preferred over DTI for the evaluation of motor and language white matter tracts in patients with intracranial masses. Results suggest that CS-DSI may be more useful than DTI for preoperative planning purposes.

Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome).

PURPOSE: To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). METHODS: We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. RESULTS: Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. CONCLUSIONS: SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions.

COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.

BACKGROUND: Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors. METHODS: One hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed. RESULTS: Multivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores. CONCLUSION: This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.

Comparison of Glioblastomas and Brain Metastases using Dynamic Contrast-Enhanced Perfusion MRI.

PURPOSE: To compare glioblastoma and brain metastases using T1-weighted dynamic contrast-enhanced (DCE)-MRI perfusion technique. METHODS: 26 patients with glioblastoma and 32 patients with metastatic brain lesions with no treatment who underwent DCE-MRI were, retrospectively, analyzed. DCE perfusion parameters K(trans) and Vp were calculated for the whole tumor. Signal intensity time curves were quantified by calculating the area under the curve (AUC) and the logarithmic slope of the washout phase to explore the heterogeneous tumor characteristics. RESULTS: Glioblastoma did not differ from all brain metastases in K(trans) (P = .34) or Vp (P = .47). Glioblastoma and melanoma metastases differed from hypovascular metastases in AUC and log slope of the washout phase of the signal intensity time curve (P < .05); however, glioblastoma and melanoma metastases did not differ from each other (AUC: P = .78, Log slope: P = .77). Glioblastoma and melanoma metastases differed from hypovascular metastases in the ratio of Voxelneg /Voxelpos (P< .03); however, they did not differ from each other. Glioblastoma and melanoma metastases differed from each other in Voxelneg_threshold at higher negative log slope threshold. CONCLUSION: DCE-MRI showed that it has a potential to differentiate glioblastomas, melanoma metastases and hypovascular brain tumors. Logarithmic slope of the washout phase and AUC of the signal intensity time curve were shown to be the best discriminator between hypervascular and hypovascular neoplasms.

Corpus Callosum Diffusion and Language Lateralization in Patients with Brain Tumors: A DTI and fMRI Study.

BACKGROUND AND PURPOSE: Examining how left-hemisphere brain tumors might impact both the microstructure of the corpus callosum (CC) as measured by fractional anisotropy (FA) values in diffusion tensor imaging (DTI) as well as cortical language lateralization measured with functional MRI (fMRI). METHODS: fMRI tasks (phonemic fluency and verb generation) were performed in order to detect activation in Broca's and Wernicke's area. Twenty patients with left-hemisphere brain tumors were investigated. fMRI results were divided into left dominant (LD), right dominant (RD), or codominant (CD) for language function. DTI was performed to generate FA maps in the anterior and posterior CC. FA values were correlated with the degree of language dominance. RESULTS: Patients who were LD or RD for language in Broca's area had lower FA in the anterior CC than those who were CD for language (median for CD = .72, LD = .66, RD = .65, P < .09). Lateralized versus CD group level analysis also showed that CD patients had higher FA in the anterior CC than patients who displayed strong lateralization in either hemisphere (median for CD = .72, lateralized = .65, P < .05). CONCLUSION: Our preliminary observations indicate that the greater FA in CD patients may reflect a more directional microstructure for the CC in this region, suggesting a greater need for interhemispheric transfer of information. Because brain tumors can cause compensatory codominance, our findings may suggest a mechanism by which interhemispheric transfer is facilitated during plasticity in the presence of a tumor.

Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases.

BACKGROUND CONTEXT: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. PURPOSE: This study aimed to identify early magnetic resonance imaging (MRI) biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. STUDY DESIGN/SETTING: This study used a retrospective case series at a large tertiary cancer center. PATIENT SAMPLE: From 2011 to 2014, 9 consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) both pre- and post-SBRT. OUTCOME MEASURE: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multiparametric magnetic resonance imaging (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. METHODS: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t tests were used to compare groups. p<.05 was deemed statistically significant. RESULTS: The median time from SBRT until posttreatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. The Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared with pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2=0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared with the mpMRI score change post-SBRT (R2=0.026). CONCLUSIONS: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at 2 months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma.

Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85% sensitivity and 79% specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69% sensitivity and 79% specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI.

Pre-operative fMRI localization of the supplementary motor area and its relationship with postoperative speech deficits.

INTRODUCTION: Neurosurgery of the supplementary motor area (SMA) is associated with transient speech defects. We investigated whether SMA laterality correlates with postoperative speech defects. MATERIALS AND METHODS: The authors reviewed 17 patients with SMA-area lesion resection and preoperative language fMRI. SMA laterality was calculated by comparison of voxel activation in paired SMAs by hand-drawn regions of interest (ROIs) (drawn by a neuroradiologist), and compared with qualitative assessment by two neuroradiologists. Postoperative speech defects before and after surgery were assessed by chart review. RESULTS: Six patients developed new speech defects that resolved within several months. Two of the patients had a pre-existing speech defect that had developed after prior SMA-area surgery. All these patients had left-sided lesions, while none of the four patients with a right-sided lesion developed a speech defect. Neuroradiologists' assessment of SMA laterality agreed with ROI calculation for the SMAs that were lateralized. However, for the SMAs in the "codominant" range by ROI, the neuroradiologists felt that all but one of the cases clearly lateralized, with the exception deemed indeterminate or codominant. No correlation between laterality of SMA and speech defect was identified. Twelve patients showed lateralization contralateral to the lesion. CONCLUSIONS: fMRI lateralization does not correlate with transient speech defects that developed from SMA-area surgery. Qualitative/visual assessment of SMA laterality was superior to ROI calculation because of the close proximity and possible overlap of signal from midline SMA. A majority of patients showed SMA lateralization contralateral to the SMA lesion.

Dynamic Contrast-Enhanced Perfusion MRI and Diffusion-Weighted Imaging in Grading of Gliomas.

PURPOSE: Accurate glioma grading is crucial for treatment planning and predicting prognosis. We performed a quantitative volumetric analysis to assess the diagnostic accuracy of histogram analysis of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) T1-weighted perfusion imaging in the preoperative evaluation of gliomas. METHODS: Sixty-three consecutive patients with pathologically confirmed gliomas who underwent baseline DWI and DCE-MRI were enrolled. The patients were classified by histopathology according to tumor grade: 20 low-grade gliomas (grade II) and 43 high-grade gliomas (grades III and IV). Volumes-of-interest were calculated and transferred to DCE perfusion and apparent diffusion coefficient (ADC) maps. Histogram analysis was performed to determine mean and maximum values for Vp and Ktrans , and mean and minimum values for ADC. Comparisons between high-grade and low-grade gliomas, and between grades II, III, and IV, were performed. A Mann-Whitney U test at a significance level of corrected P ≤ .01 was used to assess differences. RESULTS: All perfusion parameters could differentiate between high-grade and low-grade gliomas (P < .001) and between grades II and IV, grades II and III, and grades III and IV. Significant differences in minimum ADC were also found (P < .01). Mean ADC only differed significantly between high and low grades and grades II and IV (P < .01). There were no differences between grades II and III (P = .1) and grades III and IV (P = .71). CONCLUSION: When derived from whole-tumor histogram analysis, DCE-MRI perfusion parameters performed better than ADC in noninvasively discriminating low- from high-grade gliomas.

Differentiating benign from malignant vertebral fractures using T1 -weighted dynamic contrast-enhanced MRI.

PURPOSE: To differentiate pathologic from benign vertebral fractures, which can be challenging. We hypothesized that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can aid in the noninvasive distinction between pathologic and benign fractures. MATERIALS AND METHODS: Consecutive patients with vertebral fractures who underwent DCE-MRI, biopsy, and kyphoplasty were reviewed. Forty-seven fractures were separated into pathologic and benign fractures. Benign fractures were in turn separated into acute and chronic fractures for further comparison. Regions of interest (ROIs) were placed over fractured vertebral bodies. Perfusion parameters: plasma volume (Vp ), K(trans) , wash-in slope, peak enhancement, and area under the curve (AUC) were measured and compared between the three different groups of fractures. A Mann-Whitney U-test was conducted to assess the difference between the groups. RESULTS: Pathologic fractures had significantly higher (P < 0.01) perfusion parameters (Vp , K(trans) , wash-in slope, peak enhancement, and AUC) compared with benign fractures. We also found significant differences (P < 0.001) in all parameters between chronic and acute fractures. Vp and K(trans) were able to differentiate between pathologic and acute fractures (P < 0.01). No significant differences were found with peak enhancement (P = 0.21) and AUC (P = 0.4) between pathologic and acute fractures. CONCLUSION: Our data demonstrate that T1 -weighted DCE-MRI has potential to differentiate between pathologic vs. benign, acute vs. chronic, and most important, benign acute vs. pathologic vertebral fractures.

APOE polymorphisms and cognitive functions in patients with brain tumors.

OBJECTIVE: The goal of this study was to assess whether the APOE ε4 allele and other APOE single nucleotide polymorphisms (SNPs) influence neuropsychological and neuroimaging outcomes in patients with brain tumors. METHODS: Two hundred eleven patients with brain tumors participated in the study. All patients completed standardized neuropsychological tests and provided a blood sample for APOE genotyping. Ratings of white matter abnormalities were performed on MRI scans. Patients were classified into 2 groups based on the presence (n = 50) or absence (n = 161) of at least one APOE ε4 allele. Additional APOE SNPs were genotyped in a subset of 150 patients. RESULTS: Patients with at least one APOE ε4 allele had significantly lower scores in verbal learning and delayed recall, and marginally significant lower scores in executive function, in comparison to noncarriers of an ε4 allele. Patients with at least one ε4 allele and history of cigarette smoking had significantly higher scores in working memory and verbal learning than ε4 carriers who never smoked. Nine additional APOE SNPs were significantly associated with attention and executive and memory abilities. There were no significant differences between ε4 carriers and noncarriers on the extent of white matter abnormalities on MRI. CONCLUSIONS: The findings suggest that patients with brain tumors who are carriers of the APOE ε4 allele may have increased vulnerability to developing memory and executive dysfunction, and that additional SNPs in the APOE gene may be associated with cognitive outcome.