Publications by authors named "Sohil H Patel"

27 Publications

  • Page 1 of 1

Fluid attenuation in non-contrast-enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma.

J Neurooncol 2021 Mar 4. Epub 2021 Mar 4.

Department of Radiology, New York University School of Medicine, 550 1st Avenue, New York, NY, 10016, USA.

Purpose: The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma.

Methods: This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined.

Results: Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [- 0.11-1.00]), necrosis (ĸ = 0.55 [0.34-0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68-0.99]), multifocal disease (ĸ = 0.55 [0.39-0.70]), and primary lobe (ĸ = 0.85 [0.80-0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2-0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044).

Conclusions: Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant.
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http://dx.doi.org/10.1007/s11060-021-03720-yDOI Listing
March 2021

3D fast low-angle shot (FLASH) technique for 3T contrast-enhanced brain MRI in the inpatient and emergency setting: comparison with 3D magnetization-prepared rapid gradient echo (MPRAGE) technique.

Neuroradiology 2020 Oct 28. Epub 2020 Oct 28.

Department of Radiology and Medical Imaging, University of Virginia Health, PO Box 800170, Charlottesville, VA, 22908, USA.

Purpose: To retrospectively evaluate the diagnostic performance of a 1-min contrast-enhanced 3D-FLASH pulse sequence for detecting intracranial enhancing lesions compared to standard contrast-enhanced 3D-MPRAGE pulse sequence.

Methods: Contrast-enhanced 3D-FLASH (acquisition time 49 s) and contrast-enhanced 3D-MPRAGE (4 min 35 s) pulse sequences were performed consecutively in 110 inpatient/emergency department 3T MRI brain examinations and analyzed by two independent neuroradiologist readers. For each sequence, the readers recorded (1) number of enhancing intracranial lesions; (2) intracranial susceptibility artifact (presence or absence; mm depth of intracranial signal loss); and (3) motion artifact (none, mild, moderate, severe). Inter and intra-reader agreement and reader accuracy relative to a reference standard were determined, and sequence comparison with respect to susceptibility and motion artifacts was performed.

Results: There was substantial intra-reader, inter-sequence agreement [reader 1, κ = 0.70 (95% CI: [0.60, 0.81]); reader 2, κ = 0.70 (95% CI: [0.59, 0.82])] and substantial intra-sequence, inter-reader agreement [3D-MPRAGE assessment, κ = 0.76 (95% CI: [0.66, 0.86]); 3D-FLASH assessment, κ = 0.86 (95% CI: [0.77, 0.94]) for detection of intracranial enhancing lesions. For both readers, the diagnostic accuracy of 3D-FLASH and 3D-MPRAGE was similar (3D-MPRAGE: 86.4 and 88.1%; 3D-FLASH: 88.2 and 84.5%), with no inter-sequence diagnostic accuracy discordancy between the sequences for either reader. 3D-FLASH was associated with less susceptibility artifact (p < 0.001 both readers) and less motion artifact (p < 0.001 both readers).

Conclusion: On 3T brain MRI in the inpatient and emergency department setting, 1-min 3D-FLASH pulse sequence achieved comparable diagnostic performance to 4.5 min 3D-MPRAGE pulse sequence for detecting enhancing intracranial lesions, with reduced susceptibility and motion artifacts.
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http://dx.doi.org/10.1007/s00234-020-02590-xDOI Listing
October 2020

Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2-FLAIR mismatch sign.

J Neurooncol 2020 Sep 9;149(2):325-335. Epub 2020 Sep 9.

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, 22908, USA.

Purpose: The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG.

Methods: Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10mm/s (V), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach.

Results: V classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with V ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign-all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited V ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign.

Conclusion: Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with V achieving > 90% classification specificity in both internal and validation cohorts. V exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.
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http://dx.doi.org/10.1007/s11060-020-03611-8DOI Listing
September 2020

Extracting diffusion tensor fractional anisotropy and mean diffusivity from 3-direction DWI scans using deep learning.

Magn Reson Med 2021 02 18;85(2):845-854. Epub 2020 Aug 18.

Department of Radiology, University of Virginia, Charlottesville, Virginia, USA.

Purpose: To develop and evaluate machine-learning methods that reconstruct fractional anisotropy (FA) values and mean diffusivities (MD) from 3-direction diffusion MRI (dMRI) acquisitions.

Methods: Two machine-learning models were implemented to map undersampled dMRI signals with high-quality FA and MD maps that were reconstructed from fully sampled DTI scans. The first model was a previously described multilayer perceptron (MLP), which maps signals and FA/MD values from a single voxel. The second was a convolutional neural network U-Net model, which maps dMRI slices to full FA/MD maps. Each method was trained on dMRI brain scans (N = 46), and reconstruction accuracies were compared with conventional linear-least-squares (LLS) reconstructions.

Results: In an independent testing cohort (N = 20), 3-direction U-Net reconstructions had significantly lower absolute FA error than both 3-direction MLP (U-Net : 0.06 ± 0.01 vs. MLP : 0.08 ± 0.01, P < 1 × 10 ) and 6-direction LLS (LLS : 0.09 ± 0.03, P = 1 × 10 ). The MD errors were not significantly different among 3-direction MLP (0.06 ± 0.01 × 10 mm /s), 3-direction U-Net (0.06 ± 0.01 × 10 mm /s), and 6-direction LLS (0.07 ± 0.02 × 10 mm /s, P > .1).

Conclusion: The proposed U-Net model reconstructed FA from 3-direction dMRI scans with improved accuracy compared with both a previously described MLP approach and LLS fitting from 6-direction scans. The MD reconstruction accuracies did not differ significantly between reconstructions.
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http://dx.doi.org/10.1002/mrm.28470DOI Listing
February 2021

Brain Tumor Segmentation Using an Ensemble of 3D U-Nets and Overall Survival Prediction Using Radiomic Features.

Front Comput Neurosci 2020 8;14:25. Epub 2020 Apr 8.

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States.

Accurate segmentation of different sub-regions of gliomas such as peritumoral edema, necrotic core, enhancing, and non-enhancing tumor core from multimodal MRI scans has important clinical relevance in diagnosis, prognosis and treatment of brain tumors. However, due to the highly heterogeneous appearance and shape of these tumors, segmentation of the sub-regions is challenging. Recent developments using deep learning models has proved its effectiveness in various semantic and medical image segmentation tasks, many of which are based on the U-Net network structure with symmetric encoding and decoding paths for end-to-end segmentation due to its high efficiency and good performance. In brain tumor segmentation, the 3D nature of multimodal MRI poses challenges such as memory and computation limitations and class imbalance when directly adopting the U-Net structure. In this study we aim to develop a deep learning model using a 3D U-Net with adaptations in the training and testing strategies, network structures, and model parameters for brain tumor segmentation. Furthermore, instead of picking one best model, an ensemble of multiple models trained with different hyper-parameters are used to reduce random errors from each model and yield improved performance. Preliminary results demonstrate the effectiveness of this method and achieved the 9th place in the very competitive 2018 Multimodal Brain Tumor Segmentation (BraTS) challenge. In addition, to emphasize the clinical value of the developed segmentation method, a linear model based on the radiomics features extracted from segmentation and other clinical features are developed to predict patient overall survival. Evaluation of these innovations shows high prediction accuracy in both low-grade glioma and glioblastoma patients, which achieved the 1st place in the 2018 BraTS challenge.
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http://dx.doi.org/10.3389/fncom.2020.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158872PMC
April 2020

Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data.

Neuro Oncol 2020 10;22(10):1536-1544

Department of Neurology, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Background: Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated.

Methods: We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients with MBL diagnoses, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Interobserver agreement, objective response (OR) rates, and progression-free survival (PFS) were calculated. Landmark analyses were performed for OR and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazards models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed.

Results: The median follow-up time was 4.0 years. In all patients, the OR rate was .0.565 (95% CI: 0.505-0.625) by RAPNO. The interobserver agreement of OR determination between 2 raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic = 0.815; P < 0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS (hazard ratios [HRs] for 1-year landmark: OR HR = 0.079, P < 0.001; PFS HR = 10.192, P < 0.001). In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities.

Conclusion: RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.
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http://dx.doi.org/10.1093/neuonc/noaa072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566367PMC
October 2020

"Real world" use of a highly reliable imaging sign: "T2-FLAIR mismatch" for identification of IDH mutant astrocytomas.

Neuro Oncol 2020 07;22(7):936-943

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

AbstractThe T2-FLAIR (fluid attenuated inversion recovery) mismatch sign is an easily detectable imaging sign on routine clinical MRI studies that suggests diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted gliomas. Multiple independent studies show that the T2-FLAIR mismatch sign has near-perfect specificity, but low sensitivity for diagnosing IDH-mutant astrocytomas. Thus, the T2-FLAIR mismatch sign represents a non-invasive radiogenomic diagnostic finding with potential clinical impact. Recently, false positive cases have been reported, many related to variable application of the sign's imaging criteria and differences in image acquisition, as well as to differences in the included patient populations. Here we summarize the imaging criteria for the T2-FLAIR mismatch sign, review similarities and differences between the multiple validation studies, outline strategies to optimize its clinical use, and discuss potential opportunities to refine imaging criteria in order to maximize its impact in glioma diagnostics.
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http://dx.doi.org/10.1093/neuonc/noaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339896PMC
July 2020

Clinical and Radiographic Response of Leptomeningeal and Brain Metastases to Encorafenib and Binimetinib in a Patient With BRAF V600E-Mutated Lung Adenocarcinoma.

J Thorac Oncol 2019 12;14(12):e269-e271

Division of Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, Virginia. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2019.07.019DOI Listing
December 2019

MRI and CT Identify Isocitrate Dehydrogenase -Mutant Lower-Grade Gliomas Misclassified to 1p/19q Codeletion Status with Fluorescence in Situ Hybridization.

Radiology 2020 01 12;294(1):160-167. Epub 2019 Nov 12.

From the Department of Radiology and Medical Imaging (S.H.P., P.P.B., T.J.D.), Department of Pathology, Divisions of Neuropathology and Molecular Diagnostics (E.K.S.M., M.B.S.L., E.S.W.), Department of Neurology, Division of Neuro-Oncology (D.S., C.E.F.), and Department of Public Health Sciences (J.T.P.), University of Virginia Health System, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology and Neurosurgery, NYU Langone Medical Center, New York, NY (R.J.).

Background Fluorescence in situ hybridization (FISH) is a standard method for 1p/19q codeletion testing in diffuse gliomas but occasionally renders erroneous results. Purpose To determine whether MRI/CT analysis identifies isocitrate dehydrogenase ()-mutant gliomas misassigned to 1p/19q codeletion status with FISH. Materials and Methods Data in patients with -mutant lower-grade gliomas (World Health Organization grade II/III) and 1p/19q codeletion status determined with FISH that were accrued from January 1, 2010 to October 1, 2017, were included in this retrospective study. Two neuroradiologist readers analyzed the pre-resection MRI findings (and CT findings, when available) to predict 1p/19q status (codeleted or noncodeleted) and provided a prediction confidence score (1 = low, 2 = moderate, 3 = high). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was calculated. For gliomas where consensus neuroradiologist 1p/19q prediction differed from the FISH result and consensus neuroradiologist confidence score was 2 or greater, further 1p/19q testing was performed with chromosomal microarray analysis (CMA). Nine control specimens were randomly chosen from the remaining study sample for CMA. Percentage concordance between FISH and CMA among the CMA-tested cases was calculated. Results A total of 112 patients (median age, 38 years [interquartile range, 31-51 years]; 57 men) were evaluated (112 gliomas). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was 84.8% (95 of 112; 95% confidence interval: 76.8%, 90.9%). Among the 17 neuroradiologist-FISH discordances, there were nine gliomas associated with a consensus neuroradiologist confidence score of 2 or greater. In six (66.7%) of these nine gliomas, the 1p/19q codeletion status as determined with CMA disagreed with the FISH result and agreed with the consensus neuroradiologist prediction. For the nine control specimens, there was 100% agreement between CMA and FISH for 1p/19q determination. Conclusion MRI and CT analysis can identify diffuse gliomas misassigned to 1p/19q codeletion status with fluorescence in situ hybridization (FISH). Further molecular testing should be considered for gliomas with discordant neuroimaging and FISH results. © RSNA, 2019
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http://dx.doi.org/10.1148/radiol.2019191140DOI Listing
January 2020

Anatomic and Thermometric Analysis of Cranial Nerve Palsy after Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy.

Oper Neurosurg (Hagerstown) 2020 06;18(6):684-691

Department of Neurosurgery, School of Medicine, Stanford University, Stanford, California.

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive therapy for treating medication-resistant mesial temporal lobe epilepsy. Cranial nerve (CN) palsy has been reported as a procedural complication, but the mechanism of this complication is not understood.

Objective: To identify the cause of postoperative CN palsy after LITT.

Methods: Four medial temporal lobe epilepsy patients with CN palsy after LITT were identified for comparison with 22 consecutive patients with no palsy. We evaluated individual variation in the distance between CN III and the uncus, and CN IV and the parahippocampal gyrus using preoperative T1- and T2-weighted magnetic resonance (MR) images. Intraoperative MR thermometry was used to estimate temperature changes.

Results: CN III (n = 2) and CN IV palsies (n = 2) were reported. On preoperative imaging, the majority of identified CN III (54%) and CN IV (43%) were located within 1 to 2 mm of the uncus and parahippocampal gyrus tissue border, respectively. Affected CN III and CN IV were more likely to be found < 1 mm of the tissue border (PCNIII = .03, PCNIV < .01; chi-squared test). Retrospective assessment of thermal profile during ablation showed higher temperature rise along the mesial temporal lobe tissue border in affected CNs than unaffected CNs after controlling for distance (12.9°C vs 5.8°C; P = .03; 2-sample t-test).

Conclusion: CN palsy after LITT likely results from direct heating of the respective CN running at extreme proximity to the mesial temporal lobe. Low-temperature thresholds set at the border of the mesial temporal lobe in patients whose CNs are at close proximity may reduce this risk.
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http://dx.doi.org/10.1093/ons/opz279DOI Listing
June 2020

Oligodendroglioma confers higher risk of radiation necrosis.

J Neurooncol 2019 Nov 23;145(2):309-319. Epub 2019 Sep 23.

Department of Neurology, Division of Neuro-Oncology, University of Virginia Health System, P.O. Box 800432, Charlottesville, VA, 22908, USA.

Background: Radiation therapy (RT) remains a mainstay for the treatment of lower grade gliomas. Radiation neurotoxicity is a serious complication, carrying high morbidity in the absence of tumor progression. The incidence remains poorly categorized and known risk factors identified are related to the radiation modality. We hypothesized that patients with oligodendroglioma have a higher risk of radiation necrosis (RN) as compared to patients with astrocytoma.

Methods: We conducted a retrospective review of adults with lower grade diffuse gliomas over a 10-year span. The primary outcome was RN, either pathologically confirmed or clinically diagnosed. Cases without pathological confirmation must have been symptomatic, requiring administration of bevacizumab or high-dose steroids. Cox proportional hazard ratios were used for multivariate analyses.

Results: In 319 patients, we identified RN in 41 patients (12.9%): 28 patients (21.3%) with oligodendroglioma and 13 (6.9%) with astrocytoma (HR 3.42, p < 0.001). Patients with oligodendroglioma who received > 54 Gy had a higher incidence (31.2%) than those receiving ≤ 54 Gy (14.3%, HR 6.9, p = 0.002). There was no similar correlation among patients with astrocytoma. There was no difference in incidence based on use of concomitant temozolomide. Radiation necrosis appeared within 24 months from radiation in 80.5% of patients.

Conclusion: Our study suggests that patients with oligodendroglioma are at higher risk of developing RN. The incidence increases with increasing radiation dose in patients with oligodendroglioma but not with astrocytoma. RN usually appears within 24 months from RT. Patients with oligodendroglioma receiving > 54 Gy are at highest risk.
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http://dx.doi.org/10.1007/s11060-019-03297-7DOI Listing
November 2019

Increased intratumoral infiltration in IDH wild-type lower-grade gliomas observed with diffusion tensor imaging.

J Neurooncol 2019 Nov 17;145(2):257-263. Epub 2019 Sep 17.

Department of Radiology, University of Virginia, Charlottesville, VA, 22908, USA.

Purpose: Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) gene mutations (IDH) have a distinct survival advantage compared with IDH wild-type (IDH) cases but the mechanism underlying this disparity is not well understood. Diffusion Tensor Imaging (DTI) has identified infiltrated non-enhancing tumor regions that are characterized by low isotropic (p) and high anisotropic (q) diffusion tensor components that associate with poor survival in glioblastoma. We hypothesized that similar regions are more prevalent in IDH (vs. IDH) LGG.

Methods: p and q maps were reconstructed from preoperative DTI scans in N = 41 LGG patients with known IDH mutation and 1p/19q codeletion status. Enhancing and non-enhancing tumor volumes were autosegmented from standard (non-DTI) MRI scans. Percentage non-enhancing tumor volumes exhibiting low p and high q (V) were then determined using threshold values (p = 2 × 10mm/s, q = 3 × 10 mm/s) and compared between IDH and IDH LGG, and between IDH LGG with and without 1p/19q codeletion.

Results: V volumes were significantly larger in IDH LGG than in IDH LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P < 0.001). V volumes did not significantly differ between IDH LGG with and without 1p/19q codeletion (17.1 ± 9.5% vs. 14.8 ± 5.8%, P = 1.0).

Conclusion: IDH LGG exhibited larger volumes with suppressed isotropic diffusion (p) and high anisotropic diffusion (q) which reflects regions with increased cell density but non-disrupted neuronal structures. This may indicate a greater prevalence of infiltrative tumor in IDH LGG.
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http://dx.doi.org/10.1007/s11060-019-03291-zDOI Listing
November 2019

Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma.

J Neurooncol 2019 Sep 9;144(3):563-572. Epub 2019 Aug 9.

Department of Neurology, Division of Neuro-Oncology, University of Virginia Health System, P.O. Box 800432, Charlottesville, VA, 22908, USA.

Introduction: We conducted a phase Ib study (NCT02345824) to determine whether ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), penetrates tumor tissue and modulates downstream signaling pathways including retinoblastoma protein (Rb) in patients with recurrent glioblastoma (GBM).

Methods: Study participants received ribociclib (600 mg QD) for 8-21 days before surgical resection of their recurrent GBM. Total and unbound concentrations of ribociclib were measured in samples of tumor tissue, plasma, and cerebrospinal fluid (CSF). We analyzed tumor specimens obtained from the first (initial/pre-study) and second (recurrent/on-study) surgery by immunohistochemistry for Rb status and downstream signaling of CDK4/6 inhibition. Participants with Rb-positive recurrent tumors continued ribociclib treatment on a 21-day-on, 7-day-off schedule after surgery, and were monitored for toxicity and disease progression.

Results: Three participants with recurrent Rb-positive GBM participated in this study. Mean unbound (pharmacologically active) ribociclib concentrations in plasma, CSF, MRI-enhancing, MRI-non-enhancing, and tumor core regions were 0.337 μM, 0.632 μM, 1.242 nmol/g, 0.484 nmol/g, and 1.526 nmol/g, respectively, which exceeded the in vitro IC (0.04 μM) for inhibition of CDK4/6 in cell-free assay. Modulation of pharmacodynamic markers of ribociclib CDK 4/6 inhibition in tumor tissues were inconsistent between study participants. No participants experienced serious adverse events, but all experienced early disease progression.

Conclusions: This study suggests that ribociclib penetrated recurrent GBM tissue at concentrations predicted to be therapeutically beneficial. Our study was unable to demonstrate tumor pharmacodynamic correlates of drug activity. Although well tolerated, ribociclib monotherapy seemed ineffective for the treatment of recurrent GBM.
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http://dx.doi.org/10.1007/s11060-019-03258-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863163PMC
September 2019

MR imaging phenotype correlates with extent of genome-wide copy number abundance in IDH mutant gliomas.

Neuroradiology 2019 Sep 27;61(9):1023-1031. Epub 2019 May 27.

Department of Pathology, NYU School of Medicine, New York, NY, USA.

Purpose: There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features.

Methods: Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II-IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with > 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis.

Results: There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393).

Conclusions: Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas.
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http://dx.doi.org/10.1007/s00234-019-02219-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587301PMC
September 2019

There is an exception to every rule-T2-FLAIR mismatch sign in gliomas.

Neuroradiology 2019 Feb 18;61(2):225-227. Epub 2018 Dec 18.

Department of Radiology, New York University School of Medicine, New York, NY, USA.

The T2-FLAIR mismatch sign, in which a low-grade glioma is hyperintense on T2-weighted MR and centrally hypointense on T2-weighted FLAIR MR, has been reported as 100% specific for IDH-mutant astrocytomas in several series. We report several cases of "false positive" T2-FLAIR mismatch sign occurring outside the context of IDH-mutant astrocytomas, predominantly in children or young adults with pediatric-type gliomas. These results suggest caution in the interpretation of the T2-FLAIR mismatch sign in the pediatric glioma population.
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http://dx.doi.org/10.1007/s00234-018-2148-4DOI Listing
February 2019

Fundamentals of Diagnostic Error in Imaging.

Radiographics 2018 Oct;38(6):1845-1865

From the Department of Radiology, Wake Forest Baptist Medical Center, Medical Center Blvd, Winston-Salem, NC 27157-1088 (J.N.I., R.R.T.); and Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Va (R.O.M., A.J.P., S.H.P.).

Imaging plays a pivotal role in the diagnostic process for many patients. With estimates of average diagnostic error rates ranging from 3% to 5%, there are approximately 40 million diagnostic errors involving imaging annually worldwide. The potential to improve diagnostic performance and reduce patient harm by identifying and learning from these errors is substantial. Yet these relatively high diagnostic error rates have persisted in our field despite decades of research and interventions. It may often seem as if diagnostic errors in radiology occur in a haphazard fashion. However, diagnostic problem solving in radiology is not a mysterious black box, and diagnostic errors are not random occurrences. Rather, diagnostic errors are predictable events with readily identifiable contributing factors, many of which are driven by how we think or related to the external environment. These contributing factors lead to both perceptual and interpretive errors. Identifying contributing factors is one of the keys to developing interventions that reduce or mitigate diagnostic errors. Developing a comprehensive process to identify diagnostic errors, analyze them to discover contributing factors and biases, and develop interventions based on the contributing factors is fundamental to learning from diagnostic error. Coupled with effective peer learning practices, supportive leadership, and a culture of quality, this process can unquestionably result in fewer diagnostic errors, improved patient outcomes, and increased satisfaction for all stakeholders. This article provides the foundational elements for implementing this type of process at a radiology practice, with examples to help radiologists and practice leaders achieve meaningful practice improvement. RSNA, 2018.
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http://dx.doi.org/10.1148/rg.2018180021DOI Listing
October 2018

Random Versus Nonrandom Peer Review: A Case for More Meaningful Peer Review.

J Am Coll Radiol 2018 Jul 25;15(7):1045-1052. Epub 2018 May 25.

University of Virginia Health System, Charlottesville, Virginia.

Objective: Random peer review programs are not optimized to discover cases with diagnostic error and thus have inherent limitations with respect to educational and quality improvement value. Nonrandom peer review offers an alternative approach in which diagnostic error cases are targeted for collection during routine clinical practice. The objective of this study was to compare error cases identified through random and nonrandom peer review approaches at an academic center.

Methods: During the 1-year study period, the number of discrepancy cases and score of discrepancy were determined from each approach.

Results: The nonrandom peer review process collected 190 cases, of which 60 were scored as 2 (minor discrepancy), 94 as 3 (significant discrepancy), and 36 as 4 (major discrepancy). In the random peer review process, 1,690 cases were reviewed, of which 1,646 were scored as 1 (no discrepancy), 44 were scored as 2 (minor discrepancy), and none were scored as 3 or 4. Several teaching lessons and quality improvement measures were developed as a result of analysis of error cases collected through the nonrandom peer review process.

Conclusions: Our experience supports the implementation of nonrandom peer review as a replacement to random peer review, with nonrandom peer review serving as a more effective method for collecting diagnostic error cases with educational and quality improvement value.
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http://dx.doi.org/10.1016/j.jacr.2018.03.054DOI Listing
July 2018

Heuristics and Cognitive Error in Medical Imaging.

AJR Am J Roentgenol 2018 May 12;210(5):1097-1105. Epub 2018 Mar 12.

2 Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, VA 22903.

Objective: The field of cognitive science has provided important insights into mental processes underlying the interpretation of imaging examinations. Despite these insights, diagnostic error remains a major obstacle in the goal to improve quality in radiology. In this article, we describe several types of cognitive bias that lead to diagnostic errors in imaging and discuss approaches to mitigate cognitive biases and diagnostic error.

Conclusion: Radiologists rely on heuristic principles to reduce complex tasks of assessing probabilities and predicting values into simpler judgmental operations. These mental shortcuts allow rapid problem solving based on assumptions and past experiences. Heuristics used in the interpretation of imaging studies are generally helpful but can sometimes result in cognitive biases that lead to significant errors. An understanding of the causes of cognitive biases can lead to the development of educational content and systematic improvements that mitigate errors and improve the quality of care provided by radiologists.
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http://dx.doi.org/10.2214/AJR.17.18907DOI Listing
May 2018

Dynamic Contrast-Enhanced MR Imaging in Head and Neck Cancer.

Magn Reson Imaging Clin N Am 2018 Feb 21;26(1):135-149. Epub 2017 Oct 21.

Department of Radiology and Medical Imaging, University of Virginia Health System, PO Box 800170, 1215 Lee Street, Charlottesville, VA 22908, USA. Electronic address:

Dynamic contrast-enhanced (DCE) MR imaging uses rapid sequential MR image acquisition before, during, and after intravenous contrast administration to elucidate information on the microvascular biologic function of tissues. The derived pharmacokinetic parameters provide useful information on tissue perfusion and permeability that may help to evaluate entities that otherwise appear similar by conventional imaging. When specifically applied to the evaluation of head and neck cancer, DCE-MR imaging may provide valuable information to help predict treatment response, discriminate between posttreatment changes and residual tumor, and discriminate between various head and neck neoplasms.
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http://dx.doi.org/10.1016/j.mric.2017.08.008DOI Listing
February 2018

T2-FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade Gliomas: A TCGA/TCIA Project.

Clin Cancer Res 2017 Oct 27;23(20):6078-6085. Epub 2017 Jul 27.

Department of Radiology, NYU Langone Medical Center, New York, New York.

Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes. MRI scans from the TCGA/TCIA lower grade glioma database ( = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort ( = 82) was analyzed to validate the T2-FLAIR mismatch sign. Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [ = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [ = 0.728 (0.538-0.918)], lesion margins [ = 0.292 (0.135-0.449)], and peritumoral edema [ = 0.173 (0.096-0.250)]. All 15 cases that were positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2-FLAIR mismatch sign [ = 0.747 (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.00001; PPV = 100%, NPV = 76%). Among lower-grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the -mutant, 1p/19q non-codeleted molecular subtype. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0560DOI Listing
October 2017

Electrical stimulation and monitoring devices of the CNS: An imaging review.

J Neuroradiol 2017 Jun 7;44(3):175-184. Epub 2017 Feb 7.

Department of Radiology, San Antonio Military Medical Center, 3551, Roger Brooke Dr, Fort Sam Houston, TX 78234, United States.

Functional neurosurgery is a rapidly growing field with exciting future potential applications. This article describes currently used implanted electronic devices for neurologic stimulation and monitoring. The devices to be reviewed include invasive EEG electrodes, deep brain stimulator, motor cortex stimulator, responsive neurostimulation, osteo-integrated hearing aid, middle ear implant, cochlear implant, auditory brainstem implant, vagal nerve stimulator and spinal cord stimulator. Emphasis is placed on the normal components, function, positioning, potential complications and MRI safety of these devices. Understanding the motivations and appropriate use of these implantable devices is critical for clinical neuroradiologists to provide relevant imaging interpretation and protocols for patients and referring physicians.
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http://dx.doi.org/10.1016/j.neurad.2016.12.005DOI Listing
June 2017

Influence of clinical history on MRI interpretation of optic neuropathy.

Heliyon 2016 Sep 16;2(9):e00162. Epub 2016 Sep 16.

Department of Radiology, University of Virginia Health System, PO Box 800170, Charlottesville, VA 22908.

Background And Purpose: Clinical history is known to influence interpretation of a wide range of radiologic examinations. We sought to evaluate the influence of the clinical history on MRI interpretation of optic neuropathy.

Materials And Methods: 107 consecutive orbital MRI scans were retrospectively reviewed by three neuroradiologists. The readers independently evaluated the coronal STIR sequence for optic nerve hyperintensity and/or atrophy (yes/no) and the coronal post-contrast T1WI for optic nerve enhancement (yes/no). Readers initially evaluated the cases blinded to the clinical history. Following a two week washout period, readers again evaluated the cases with the clinical history provided. Inter-reader and reader-clinical radiologist agreement was assessed using Cohen's simple kappa coefficient.

Results: Intra-reader agreement, without and with provision of clinical history, was 0.564-0.716 on STIR and 0.270-0.495 on post-contrast T1WI. Inter-reader agreement was overall fair-moderate. On post-contrast T1WI, inter-reader agreement was significantly higher when the clinical history was provided (p = 0.001). Reader-clinical radiologist agreement improved with provision of the clinical history to the readers on both the STIR and post-contrast T1WI sequences.

Conclusions: In the MRI assessment of optic neuropathy, only modest levels of inter-reader agreement were achieved, even after provision of clinical history. Provision of clinical history improved inter-reader agreement, especially when assessing for optic nerve enhancement. These findings confirm the subjective nature of orbital MRI interpretation in cases of optic neuropathy, and point to the importance of an accurate clinical history. Of note, the accuracy of orbital MRI in the context of optic neuropathy was not assessed, and would require further investigation.
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http://dx.doi.org/10.1016/j.heliyon.2016.e00162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035347PMC
September 2016

MRI of a syrinx: is contrast material always necessary?

AJR Am J Roentgenol 2015 May;204(5):1082-5

1 Department of Radiology, Division of Neuroradiology, Massachusetts General Hospital, 55 Fruit St, Gray 2, Rm 273A, Boston, MA 02114.

Objective: The workup of a syrinx often includes contrast-enhanced MRI to exclude the presence of an underlying mass. The diagnostic yield of performing these additional contrast-enhanced sequences is not well defined in the literature. We hypothesized that T2-weighted imaging alone could reliably exclude the presence of a syrinx-associated mass without the need for contrast-enhanced imaging sequences in all cases.

Materials And Methods: Two independent readers retrospectively analyzed contrast-enhanced MRI studies of 87 consecutive patients with syringes. The presence or absence of an associated spinal cord mass was determined using only T2-weighted imaging. The imaging features considered positive for a possible syrinx-associated lesion on T2-weighted imaging were syrinx nodularity, syrinx septations, and a spinal cord signal intensity abnormality or a mass separate from the syrinx. The size of the syrinx was also recorded. Using contrast-enhanced sequences as the reference standard, statistical analysis was performed to determine the accuracy of T2-weighted imaging in detecting a syrinx-associated mass.

Results: Of the 87 cases of syrinx, there were 23 mass lesions, 11 Chiari malformations, three spinal cord contusions, and 50 idiopathic syringes. Using T2-weighted imaging alone, readers detected no findings suspicious for a syrinx-associated mass in 55 cases and detected findings suspicious for a mass in 32 of 87 cases. Reader sensitivity for an underlying mass lesion was 100%; specificity, 86%; positive predictive value, 72%; and negative predictive value, 100%. Interreader agreement was excellent (κ = 0.88). Syrinx size showed a positive correlation with the presence of a mass lesion (p < 0.0001).

Conclusion: T2-weighted imaging alone appears to have a high sensitivity and high negative predictive value in evaluating for a syrinx-associated mass, and contrast-enhanced imaging may not be required for the workup of a syrinx.
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http://dx.doi.org/10.2214/AJR.14.13310DOI Listing
May 2015

MDCT urography with high-volume low-concentration i.v. contrast material, peroral hydration, i.v. furosemide, and i.v. saline: qualitative and quantitative assessment in 100 consecutive patients.

AJR Am J Roentgenol 2012 Jul;199(1):111-7

Department of Radiology, NYU-Langone Medical Center, 550 1st Ave, New York, NY 10016, USA.

Objective: The purpose of this study is to qualitatively and quantitatively assess MDCT urography performed with a high volume of low-concentration (240 mg I/mL) i.v. contrast agent supplemented with peroral hydration, i.v. furosemide, and i.v. saline.

Materials And Methods: This retrospective evaluation of 100 consecutive normal MDCT urograms was performed for clinical indication of hematuria; patients (76 men and 24 women) were 27-90 years old (mean [± SD] age, 60 ± 15 years). Three radiologists evaluated the degree of opacification across six urinary tract segments (for a total of 1200 measurements per radiologist) on a 4-point scale (0-3). One radiologist measured the maximum short-axis diameter of the proximal, mid, and distal ureters in each patient. Mean opacification scores were calculated for each segment. Radiologist agreement was assessed by kappa coefficient and Spearman rank correlation. Ureteral diameter was correlated to degree of opacification using the Jonckheere-Terpstra trend test. A comparison with published studies using similar scoring methods was undertaken.

Results: Of 1200 measured ureteral segments, a total of 24 among the three radiologists were reported as nonopacified. The mean opacification scores ranged from 2.63 ± 0.8 to 3.00 ± 0.8. Calculated kappa coefficients are indicative of substantial agreement (> 0.61). The mean maximal ureteral diameters were 5.44 ± 1.10, 6.32 ± 1.54, and 5.32 ± 1.55 mm for the proximal, mid, and distal ureters, respectively. For all three radiologists, the mean opacification scores increased as distention increased. The Spearman correlation and corresponding p value (p < 0.001) for the association between the distention with the opacification scores show significant correlation. The opacification scores and ureteral distention exceeded published results.

Conclusion: An MDCT urography technique using high-volume low-concentration i.v. contrast, oral and i.v. hydration, and i.v. diuretic reliably optimizes urinary tract opacification and distention. A positive correlation was found between ureteral distention and opacification.
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http://dx.doi.org/10.2214/AJR.11.7754DOI Listing
July 2012

Posttreatment recurrence of malignant brain neoplasm: accuracy of relative cerebral blood volume fraction in discriminating low from high malignant histologic volume fraction.

Radiology 2009 Mar;250(3):887-96

Division of Neuroradiology, Department of Radiology, Division of Neuro-oncology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA.

Purpose: To determine the accuracy of relative cerebral blood volume (rCBV) fraction for distinguishing high-grade recurrent neoplasm from treatment-related necrosis (TRN) in enhancing masses identified on surveillance magnetic resonance (MR) images following treatment for primary or secondary brain neoplasm.

Materials And Methods: This institutional review board approved and HIPAA-compliant retrospective study included 30 patients undergoing resection of recurrent enhancing mass appearing after treatment with surgery and radiation, with or without chemotherapy. The enhancing mass volume was manually segmented on three-dimensional T1-weighted images. The rCBV maps were created by using T2-weighted dynamic susceptibility contrast perfusion MR imaging and registered to T1-weighted images, and the fraction of enhancing mass with rCBV above a range of thresholds was calculated. A receiver operating characteristic (ROC) curve was created by calculating sensitivity-specificity pairs at each threshold for rCBV fraction (< or = 20% or > 20%) by using percentage of malignant features at histologic evaluation as the reference criterion. Relationships between rCBV and probability of recurrence were estimated by using logistic regression analysis.

Results: ROC analysis showed excellent discriminating accuracy of rCBV fraction (area under the ROC curve, 0.97 +/- 0.03 [standard error]) and high efficiency (93%) with an rCBV threshold of 1.8 times that of normal-appearing white matter. Logistic regression analysis showed that a unit increase of rCBV is associated with a 254-fold increase (95% confidence interval: 43, 1504, P < .001) of the odds that enhanced tissue is recurrence, adjusting for age, treatment, volume of enhancing tissue, and time to suspected recurrence.

Conclusion: The fraction of malignant histologic features in enhancing masses recurring after treatment for brain neoplasms can be predicted by using the rCBV fraction, with improved differentiation between recurrent neoplasm and TRN.
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http://dx.doi.org/10.1148/radiol.2502071444DOI Listing
March 2009

Whole-brain N-acetylaspartate level and cognitive performance in HIV infection.

AJNR Am J Neuroradiol 2003 Sep;24(8):1587-91

Department of Radiology, New York University School of Medicine, New York, NY, USA.

Background And Purpose: In the brain of HIV-infected patients, proton MR spectroscopic studies are typically used to examine small volumes of tissue with single-voxel methods. Since brain disease is diffuse in patients with HIV, such studies preclude assessment of the true extent of the metabolic burden. To assess this extent, the relationship between global neuronal integrity, reflected by the whole-brain N-acetylaspartate (WBNAA) concentration, was correlated with neuropsychological function and the AIDS dementia complex (ADC) stage score.

Methods: WBNAA levels were compared between 15 HIV-infected patients (seven symptomatic, eight asymptomatic) and 13 age- and sex-matched healthy subjects. The patients' WBNAA level was correlated with cognitive performance, as measured with a battery of eight tests (NPZ-8), including the ADC stage score and four total-memory, mood, motor, and processing speed subtests.

Results: WBNAA levels were significantly different between patients and healthy subjects (mean +/- sigma, 11.82 +/- 1.40 and 12.91 +/- 1.03 mmol/L, respectively; P =.032) after we adjusted for age and sex effects. Intermediate negative correlations were found between the WBNAA level, the processing speed subtest score (r = -0.50, P =.03), and the ADC stage score (r = -0.44, P =.05).

Conclusion: The WBNAA concentration complements brain atrophy data with information about the quality of the remaining neuronal and axonal tissue in patients with HIV infection. In HIV-infected patients, its correlation with processing speed and the ADC score indicates that the latter reflects pathologic deficits, which are extensive throughout the brain.
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September 2003

Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients.

AJNR Am J Neuroradiol 2002 Apr;23(4):543-9

Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

Background And Purpose: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent.

Methods: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery).

Results: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01).

Conclusion: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons.
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April 2002