T. Chenevert - Academia.edu (original) (raw)

Papers by T. Chenevert

Research paper thumbnail of Diffusion Tensor Imaging as a Biomarker for Neurotoxicity of Radiation

International Journal of Radiation Oncology*Biology*Physics, 2008

Research paper thumbnail of Abstract 4433: DW-MR imaging as a predictive biomarker of radiosensitization of GBM through targeted inhibition of checkpoint kinases

Cancer Research, 2013

Purpose: The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms ... more Purpose: The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms including checkpoint kinase (Chk1/2) mediated increased DNA repair capability which can attenuate the effects of genotoxic chemotherapies and radiation. The goal of this study was to evaluate DW-MRI as a biomarker for Chk1/2 inhibitors in combination with radiation for enhancement of treatment efficacy in GBM. Experimental Design: We evaluated a specific small molecule inhibitor of Chk1/2, AZD7762, in combination with radiation using in vitro human cell lines and in vivo using a genetically engineered GBM mouse model. Diffusion-weighted and T1-contrast MRI were used to follow treatment effects on intracranial tumor cellularity and growth rates, respectively. Results: AZD7762 inhibited clonal proliferation in a panel of GBM cell lines and increased radiosensitivity in p53-mutated GBM cell lines to a greater extent compared to p53-wild type cells. In vivo efficacy of AZD7762 demonstrated a...

Research paper thumbnail of MR Evaluation of Liver Iron Overload

Journal of Computer Assisted Tomography, 1988

Research paper thumbnail of Prognostic Value of Cerebral Blood Volume by MR Perfusion Imaging in High-Grade Gliomas Prior to and During Early Course of RT

International Journal of Radiation Oncology*Biology*Physics, 2005

Research paper thumbnail of Error Reduction in Through Transmission Tomography Using Large Receiving Arrays with Phase-Insensitive Signal Processing

IEEE Transactions on Sonics and Ultrasonics, 1984

Akrrucr-In order to reduce artifacts due to nonstraight line wave propagation in ultrasonic compu... more Akrrucr-In order to reduce artifacts due to nonstraight line wave propagation in ultrasonic computed tomography of attenuation, the use of an experimental receiving array with phase-insensitive signal processing was evaluated. A 46-element 2.25 MHz array receiver having a singleelement aperture of 1.2 mm X 1.2 mm and a center-to-center spacing of 1.4 mm was employed and projections were taken of a phantom whose refraction characteristics were controlled by temperature. Array signals were processed incoherently and attenuation projections were calculated according to the energy ratio, frequency shift, and log spectral difference methods. The resulting projections then were compared to those obtained by a 19 mm diameter 35 MHz phasesensitive single-element receiver. The phase-insensitive array response was superior to the phase-sensitive singleelement receiver, especially when the phantom became refractive. Modest improvements in the reduction of refractive errors were obtained using the energy ratio method and negligible refractive errors were observed when the frequency shift or the log spectral difference method was used.

Research paper thumbnail of Lower Baseline Apparent Diffusion Coefficient Values are Associated with Worse Survival in Locally Advanced Pancreatic Cancer

International Journal of Radiation Oncology*Biology*Physics, 2020

Research paper thumbnail of Abstract W P248: Cerebral Tissue Iron Quantification on MRI Following Intracerebral Hemorrhage

Stroke, 2014

Purpose: Intracerebral hemorrhage (ICH) is a fatal subtype of Hemorrhagic stroke. Tissue iron at ... more Purpose: Intracerebral hemorrhage (ICH) is a fatal subtype of Hemorrhagic stroke. Tissue iron at the periphery of ICH has been demonstrated to be neurotoxic in animal models. No robust method to quantify tissue iron following ICH currently exists. Our aim is to determine a robust algorithm based on MRI to quantify tissue iron in the wake of ICH. Methods: Following Institutional review board approval we constructed an MRI phantom. Eight 4 cc vials with 50 % decreasing dilutions of Ferraheme (iron for IV therapy) were prepared starting from 0.6 mg/ml ending at 0.005 mg/ml. The vials were stuck to the undersurface of the lid of a water bath container and scanned in a 3T MRI with T2* sequences. The T2* signal magnitudes were calculated for each concentration. Subsequently a human control brain and two patients with left basal ganglia ICH were scanned with identical parameters. The T2* signal magnitude was calculated at 3 ROIs at the periphery of the ICH. Results: The R2* maps demonstrat...

Research paper thumbnail of E-086 Human intracerebral hemorrhage (ICH): Early hemolysis/erythryolysis, iron overload, perihematomal edema surviving white matter; translational evidence for brain tissue injury markers on MRI

Electronic poster abstracts, 2021

Results We identified 111 patients between 2017 and 2020, 57 patients required a drip (43 NCR, 14... more Results We identified 111 patients between 2017 and 2020, 57 patients required a drip (43 NCR, 14 CLV), and 54 patients were managed with prn medications. Median NIHSS was higher in the drip group (18, IQR 13-21) vs. 15.5 (IQR 9-20), p value= 0.03. There was no significant difference in the rate of good clinical outcome defined as mRs of 0-2 or return to baseline (47.4 vs 61.1%, p value=0.18); rate of any HI (29.8% vs. 27.8%, p value=0.84) and sICH(5.3% vs 0%, p value=0.24) between the two groups (drip vs. no drip). When comparing the NCR to CLV groups, median ROBP was significantly shorter in the CLV group, 5min (IQR 0.75-7) vs. 17min (IQR 6-35), p value= 0.003; and total duration of time outside the pre-specified BP range was 37.5 min (IQR 19-120) vs. 118 min (57-227) consecutively, p value=0.045. HT rates (14.3% vs. 34.9%, p value=0.19), sICH rates (0 vs. 7%, p value=0.57), and rate of good clinical outcome (64.3% vs. 41.9%, p value=0.22) were similar between the two groups (CLV vs. NCR). In a Multivariate analysis, after adjusting for age, gender, IV tPA administration, drip used and time out of range; NIHSS (OR 0.8, CI 0.70-0.91, p=0.0008) and ROBP (OR=1.05, CI 1.0-1.1, p value=0.032) were independent predictors of good clinical outcome. Conclusion CLV achieved faster ROBP time and better BP control after MT. Further prospective studies are needed.

Research paper thumbnail of O-022 White matter survival within and around the hematoma: quantification by MRI in patients with intracerebral hemorrhage

Oral abstracts, 2021

scans; and 4. Motion compensation post-processing algorithm technology. Methods Patients with AIS... more scans; and 4. Motion compensation post-processing algorithm technology. Methods Patients with AIS who received endovascular mechanical thrombectomy were prospectively included in this monocentric study (n=105). Study 1: Image quality of non-contrast circular CB-CT scans were analyzed using 2 quantitative and 6 qualitative measures and were compared to CT. Study 2: 6 types of image artifacts were compared between circular and dual-axis CB-CT scans. Study 3: Clot detection, ischemic core and collateral blood supply was assessed on CB-CT Perfusion imaging and compared to baseline CT and DSA imaging. Study 4: Motion artifacts were assessed on all scans before and after post-processed using a motion artifact correction algorithm. Results Study 1: Newer non-contrast CB-CT circular scans had higher mean contrast-to-noise ratio and lower mean image noise compared to older generation protocols. The largest image quality improvements included grey/white matter differentiation (59% improvement), and reduction of image noise and artefacts (63% & 50% improvement, respectively). Study 2: Dual-axis CB-CT scans had significantly improved beam hardening and cone-beam artifacts compared to circular scans. Study 3: CB-CT stroke perfusion imaging software accurately demonstrates vessel patency, ischemic core, and collateral blood supply. Study 4: 51% of all AIS CB-CT scans had motion artifacts, of which 91% improved after post-processing with our motion correction algorithm. Overall 76% of the scans were sufficient for clinical decision making prior to correction, which improved to 93% after post processing with our algorithm. Conclusions The latest generation of CB-CT scans & technology allow for exclusion of haemorrhages, stroke core definition and demonstration of brain perfusion and collaterals. These improvements suggest that CB-CT is acceptable for emergency stroke imaging assessment before mechanical thrombectomy, which may reduce door-to-groin puncture times and improve patient outcomes.

Research paper thumbnail of Radiotherapy (RT) Dose-intensification (DI) Using Intensity-modulated RT (IMRT) versus Standard-dose (SD) RT with Temozolomide (TMZ) in Newly Diagnosed Glioblastoma (GBM): Preliminary Results of NRG Oncology BN001

International Journal of Radiation Oncology*Biology*Physics, 2020

of upfront SRS remains controversial because of lack of randomized evidence. Materials/Methods: I... more of upfront SRS remains controversial because of lack of randomized evidence. Materials/Methods: In this phase III randomized controlled trial (NCT01592968), adult patients with 4-15 untreated non-melanoma BMs were stratified by histology, number of lesions, baseline Hopkins Verbal Learning Test-Revised Total Recall (HVLT-R TR) score, extracranial disease, KPS, and age, and randomly assigned to SRS or WBRT. Memantine was encouraged in the WBRT arm after publication of RTOG 0614. Prior SRS to 1-3 BMs with at least 3 months (mos) interval was allowed. Test of neurocognitive function (NCF) were completed at baseline and longitudinally including tests of learning and memory (HVLT-R), verbal fluency (Controlled Oral Word Association (COWA), and processing speed and executive function (Trail Making Test Parts A [TMTA] and B [TMTB]). Primary endpoints were HVLT-R TR and local control (LC) at 4 mos. Secondary endpoints included additional NCF tests, overall survival (OS), distant brain failure, toxicity, and time to systemic therapy. The trial was terminated early due to slow accrual. Results: Between 09/2012 and 09/2019, 72 patients were randomized to SRS (n Z 36) or WBRT (n Z 36) with an estimated median follow-up time of 6.6 mos (range 0.2-69.8). Median number of BMs at enrollment was 8. Thirty-one patients were evaluable for HVLT-R TR at 4 mos. In the WBRT arm, 62% of patients received memantine. In the primary endpoint analysis, relative to baseline, the 4 mo HVLT-R TR standardized z-score increased by +0.21 (standard error [SE] 0.27) for SRS-treated patients and declined by-0.74 (SE 0.36) for WBRT-treated patients (p Z 0.041). Based on the Clinical Trial Battery Composite (the mean z-score for the HVLT-R, COWA, TMT), at 4 mos the NCF of patients in the SRS arm improved on average +0.23 (SE 0.14) and the NCF of patients in the WBRT arm declined on average-0.73 (SE 0.35), p Z 0.008. Median OS time was 10.4 mos for SRS and 8.4 mos for WBRT (p Z 0.45). Preliminary analyses of LC at 4 mos demonstrated 100% LC rate for SRS and 95.5% for WBRT (p Z 0.53), and median time to distant brain failure (DBF) was 4.3 mos for SRS vs.18.1 mos for WBRT (p Z 0.09). LC and DBF results are being independently confirmed by the trial radiologist presently. Conclusion: In non-melanoma patients with 4-15 brain metastases, SRS was associated with reduced risk of neurocognitive deterioration relative to WBRT without compromising OS. These results provide level 1 evidence to support the use of SRS in patients with 4-15 brain metastases amenable to SRS.

Research paper thumbnail of O-006 Histotripsy for intracerebral hemorrhage in a porcine model

Oral Abstracts, 2020

applicable in the US. This study prospectively validates the RACE scale as administered by US-bas... more applicable in the US. This study prospectively validates the RACE scale as administered by US-based EMS personnel in the pre-hospital setting and we compare our results to the originally published results. Methods 232 adult patients suspected of having a stroke by EMS and transported to a participating comprehensive stroke center had the RACE scale administered prospectively and recorded in a secure web-based database. Admission NIHSS score and final diagnosis were recorded. Cerebrovascular imaging studies (CTA, MRA or DSA) were reviewed by a blinded, independent Neuroradiologist to determine LVO diagnosis. We used SAS and c-statistics to create receiver operating characteristic (ROC) curves to determine the area under the curve (AUC) and optimal cut point (CP) scores for the RACE scale. We also calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy for the optimal CP score. Results Our analysis of the predictive capability of the RACE scale showed similar predictive capacities for radiographicallyconfirmed LVO in patients prospectively tested in the US as compared to the original Spanish RACE scale population. The best CP score value predictive of LVO in our US-RACE study was determined to be !6, compared to the original Spanish study which was !5 (table 1). The overall prevalence of LVO as defined in our study was 13.4%, compared to a prevalence of 21.3% for the original paper's definition of LVO. Conclusion This is the first prospective validation of the RACE scale performed in the US. These results demonstrate that the RACE scale retains the previously published predictive value in both the US and Spain in accurately identifying LVO stroke in a prehospital setting by EMS.

Research paper thumbnail of Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives

European Radiology, 2017

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic in... more For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials Contribution of NIST-not subject to copyright in the US * N. M. deSouza

Research paper thumbnail of A Flexible Spline Model of the Spin Echo with Applications to Estimation of the Spin-Spin Relaxation Time

Journal of Magnetic Resonance, Series A, 1994

Research paper thumbnail of Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis

British journal of cancer, Jan 18, 2017

Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadj... more Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC. Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest ...

Research paper thumbnail of TU-C-12A-08: Thermally-Stabilized Isotropic Diffusion Phantom for Multisite Assessment of Apparent Diffusion Coefficient Reproducibilty

Medical Physics, 2014

PURPOSE To construct an appropriate phantom for quality control use in diffusion-weighted imaging... more PURPOSE To construct an appropriate phantom for quality control use in diffusion-weighted imaging (DWI), to establish ground truth for measurement of apparent diffusion coefficient (ADC) and to characterize measurement linearity across a relevant physiological range of ADC. METHODS Aqueous solutions containing the polymer polyvinylpyrrolidone (PVP) were mixed at concentrations of 0, 10, 20, 30, 40 and 50% by mass PVP. These solutions were placed in 20 mL vials, arranged in concentric inner and outer circles, with a central water vial, and were fixed in a spherical phantom with a diameter of 194 mm, designed to fit into commercially-available MRI head coils. Two prototype phantoms were constructed, and underwent inter-site comparison in the US and EU. The phantoms were filled with an ice-water bath to ensure stable temperature; 0 °C temperature was verified by use of a thermocouple before and after scans. The phantoms were scanned using b-values of 0, 500 and 900 s/mm2 at several sites, using coronal and/or axial orientations and scan planes. RESULTS ADC values ranged from 0.12 to 1.12 × 10-3 mm2 /s, and exhibited a high degree of reproducibility across different scanners and imaging sites (coefficient of variations (CoV) ranged from 1.1 to 2.2% for 0 to 40% PVP, with 50% PVP at 11.3%). Little difference in ADCs was seen between inner and outer ring vials of the same PVP concentration (average CoV< 5% across vials, 10.3% for 50% PVP). CONCLUSION The range of ADCs covers a relevant physiological range, most notably in brain white matter. The ADCs of water vials were in excellent agreement with literature values of the diffusion coefficient of water at 0 °C (1.1 × 10-3 mm2 /s). The phantom provides a much needed quality control tool for DWI, and provides ground truth with the diffusion coefficient of water at 0 °C.

Research paper thumbnail of 2134: Incorporating Individualized Target Motion and Deformation in IMRT Planning for Unresectable Pancreatic Cancer: Dosimetric Implications

medication or any grade 3-4 toxicity. SPSS software was used to calculate Kaplan-Meier survival e... more medication or any grade 3-4 toxicity. SPSS software was used to calculate Kaplan-Meier survival estimates and 2-tailed t-tests for comparisons. Results: Gastrointestinal toxicity grade 3-4 was recorded in 4.2 % of patients who received 1.8 Gy vs. 19.4% for patients who received 2.4 Gy fractions (pϭ0.05). 3/24 patients (12.5%) that received 1.8Gy fractions required a treatment break compared to 14/36 (38.8%) that received 2.4 Gy fractions (pϭ0.02). Median survival was 16.4 months 95% CI [10.3,22.4] for patients with LA disease treated with standard fractionation vs. 11.1 months 95%CI [8.2,13.9] for hypofractionation. For patients treated after Whipple resection with hypofractionation, median survival was 17.2 months and has not yet been reached for patients treated with standard fractionation. Conclusions: In comparison with hypofractionated chemoradiation with concurrent full dose gemcitabine for pancreatic cancer, standard fractionation is associated with significantly less grade III-IV gastrointestinal toxicity and fewer treatment breaks. These results suggest that dose escalation studies using standard fractions may be advantageous for pancreatic cancer.

Research paper thumbnail of 1108: Proton Magnetic Spectroscopy (1H-MRSI) of Early Versus Late Delayed Radiation-Induced Effect of Normal White Matter in Malignant Glioma Patients

Research paper thumbnail of Phase-Based Imaging of Magnetically Tagged Cells

Research paper thumbnail of TH-E-ValB-06: Quantitative Characterization of Tumor Vascular Dysfunction in High-Grade Gliomas Prior to and During Radiotherapy

Medical Physics, 2006

Introduction: Vascular properties within and adjacent to tumors may not be distinguishable by cer... more Introduction: Vascular properties within and adjacent to tumors may not be distinguishable by cerebral blood flow [CBF] or cerebral blood volume [CBV] alone, since the rates of CBV change may not be proportional in magnitude to CBF change. Hence, the empirical and physiological relationships between CBF and CBV were examined to estimate vasculature‐specific hemodynamiccharacteristics in high‐grade gliomas. Methods: Twenty patients with gliomas were studied with dynamic contrast‐enhanced T2* MRI [DCE‐MRI] before and during radiotherapy [RT]. CBF and CBV were calculated from DCE‐MRI and the relationships between the two were evaluated using two different metrics: The physiological measure of Mean Transit Time [MTT]=CBV/CBF; and, Empirical fitting of CBV and CBF using the power law, expressed as CBV=Constant*(CBF)β. Three tissue types were assessed, Gd‐enhanced tumor volume [GdTV], non‐enhancing abnormal tissue located beyond GdTV but within the abnormal hyperintense volume on FLAIR images [NEV], and normal tissue in hemisphere contralateral to tumor[CNT]. Effects of tissue types, CBV magnitudes (low[L], medium[M] and high[H] CBV), before and during RT, on MTT and β were analyzed by factorial ANOVA. Results: Both, MTT and β were significantly different (p<0.009) among the three tissue types. MTT increased from CNT(=1.60s) to NEV(=1.93s) to GdTV(=2.28s) (<0.0005). The power exponent β was significantly greater in GdTV(=1.079) and NEV(=1.070) than CNT(=1.025), but β in NEV and GdTV were not significantly different from each other. β increased with increasing CBV magnitude. There was a significant decrease in MTT and a significant increase in β in tumor (GdTV) and peritumoral (NEV) tissue during RT compared with pre‐RT values. Conclusions: β was strongly dependent on CBV magnitude and MTT on tissue type. Progressive abnormalities in functional characteristics of the vascular bed were noted, with significant disorder in tumor, but mild abnormality in peritumoral tissue. Early vascular response to radiation was first observed in functional rather than structural properties.

Research paper thumbnail of TH-D-AUD C-01: Early Blood-Brain-Barrier Disruption in Response to RT as a Biomarker for Neurotoxicity

Medical Physics, 2008

Purpose: Studies of neurocognitive dysfunction after radiation in animals suggest that vascular i... more Purpose: Studies of neurocognitive dysfunction after radiation in animals suggest that vascular injury plays a key role. We hypothesized that blood‐brain‐barrier (BBB) disruption in normal appearing cerebral tissue of patients early in the course of fractionated radiation therapy (RT) is a biomarker for delayed neurocognitive dysfunction. Method and Materials: Ten patients with low‐grade glioma, or suprasellar lesion and underwent 3D conformal cranial RT (28–33 fx of 1.8 Gy) participated in a prospective MRI study. Dynamic‐contrast enhanced (DEC) MRI was acquired before, at week 3 and week 6 during the course of, and at 1, 6 and 18 months after the completion of RT. Using the modified Toft model, the contrast transfer constant (K) from the intravascular space to the extravascular extracellular space was estimated. A battery of standardized neuropsychological tests was performed at the same times as the pre‐ and post‐RT MRI. The relationship between the temporal changes in K and the dosimetric parameters was analyzed by a linear mixed model. Correlations between the changes in K and early delayed changes in the neurocognitve functions were analyzed by linear regression.Results: The K values increased significantly in normal appearing tissue regions that received >40 Gy at week 6 during RT (p<0.05), suggesting BBB opening. The elevated K values decreased gradually after RT. The changes in K both during and after RT were significantly correlated with the doses received at the time but the significance decreased from p = 0.0001 at week 3 during RT to 0.03 at 6 months after RT. The changes in K of left frontal lobe at week 3 during RT were significantly negatively correlated with the changes in verbal learning scores at 6 months after RT (p<0.02). Conclusion: Our data suggest early BBB disruption could be a biomarker for delayed neurocognitve function deterioration. Supported by NIHP01CA59827 and R21CA11369901.

Research paper thumbnail of Diffusion Tensor Imaging as a Biomarker for Neurotoxicity of Radiation

International Journal of Radiation Oncology*Biology*Physics, 2008

Research paper thumbnail of Abstract 4433: DW-MR imaging as a predictive biomarker of radiosensitization of GBM through targeted inhibition of checkpoint kinases

Cancer Research, 2013

Purpose: The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms ... more Purpose: The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms including checkpoint kinase (Chk1/2) mediated increased DNA repair capability which can attenuate the effects of genotoxic chemotherapies and radiation. The goal of this study was to evaluate DW-MRI as a biomarker for Chk1/2 inhibitors in combination with radiation for enhancement of treatment efficacy in GBM. Experimental Design: We evaluated a specific small molecule inhibitor of Chk1/2, AZD7762, in combination with radiation using in vitro human cell lines and in vivo using a genetically engineered GBM mouse model. Diffusion-weighted and T1-contrast MRI were used to follow treatment effects on intracranial tumor cellularity and growth rates, respectively. Results: AZD7762 inhibited clonal proliferation in a panel of GBM cell lines and increased radiosensitivity in p53-mutated GBM cell lines to a greater extent compared to p53-wild type cells. In vivo efficacy of AZD7762 demonstrated a...

Research paper thumbnail of MR Evaluation of Liver Iron Overload

Journal of Computer Assisted Tomography, 1988

Research paper thumbnail of Prognostic Value of Cerebral Blood Volume by MR Perfusion Imaging in High-Grade Gliomas Prior to and During Early Course of RT

International Journal of Radiation Oncology*Biology*Physics, 2005

Research paper thumbnail of Error Reduction in Through Transmission Tomography Using Large Receiving Arrays with Phase-Insensitive Signal Processing

IEEE Transactions on Sonics and Ultrasonics, 1984

Akrrucr-In order to reduce artifacts due to nonstraight line wave propagation in ultrasonic compu... more Akrrucr-In order to reduce artifacts due to nonstraight line wave propagation in ultrasonic computed tomography of attenuation, the use of an experimental receiving array with phase-insensitive signal processing was evaluated. A 46-element 2.25 MHz array receiver having a singleelement aperture of 1.2 mm X 1.2 mm and a center-to-center spacing of 1.4 mm was employed and projections were taken of a phantom whose refraction characteristics were controlled by temperature. Array signals were processed incoherently and attenuation projections were calculated according to the energy ratio, frequency shift, and log spectral difference methods. The resulting projections then were compared to those obtained by a 19 mm diameter 35 MHz phasesensitive single-element receiver. The phase-insensitive array response was superior to the phase-sensitive singleelement receiver, especially when the phantom became refractive. Modest improvements in the reduction of refractive errors were obtained using the energy ratio method and negligible refractive errors were observed when the frequency shift or the log spectral difference method was used.

Research paper thumbnail of Lower Baseline Apparent Diffusion Coefficient Values are Associated with Worse Survival in Locally Advanced Pancreatic Cancer

International Journal of Radiation Oncology*Biology*Physics, 2020

Research paper thumbnail of Abstract W P248: Cerebral Tissue Iron Quantification on MRI Following Intracerebral Hemorrhage

Stroke, 2014

Purpose: Intracerebral hemorrhage (ICH) is a fatal subtype of Hemorrhagic stroke. Tissue iron at ... more Purpose: Intracerebral hemorrhage (ICH) is a fatal subtype of Hemorrhagic stroke. Tissue iron at the periphery of ICH has been demonstrated to be neurotoxic in animal models. No robust method to quantify tissue iron following ICH currently exists. Our aim is to determine a robust algorithm based on MRI to quantify tissue iron in the wake of ICH. Methods: Following Institutional review board approval we constructed an MRI phantom. Eight 4 cc vials with 50 % decreasing dilutions of Ferraheme (iron for IV therapy) were prepared starting from 0.6 mg/ml ending at 0.005 mg/ml. The vials were stuck to the undersurface of the lid of a water bath container and scanned in a 3T MRI with T2* sequences. The T2* signal magnitudes were calculated for each concentration. Subsequently a human control brain and two patients with left basal ganglia ICH were scanned with identical parameters. The T2* signal magnitude was calculated at 3 ROIs at the periphery of the ICH. Results: The R2* maps demonstrat...

Research paper thumbnail of E-086 Human intracerebral hemorrhage (ICH): Early hemolysis/erythryolysis, iron overload, perihematomal edema surviving white matter; translational evidence for brain tissue injury markers on MRI

Electronic poster abstracts, 2021

Results We identified 111 patients between 2017 and 2020, 57 patients required a drip (43 NCR, 14... more Results We identified 111 patients between 2017 and 2020, 57 patients required a drip (43 NCR, 14 CLV), and 54 patients were managed with prn medications. Median NIHSS was higher in the drip group (18, IQR 13-21) vs. 15.5 (IQR 9-20), p value= 0.03. There was no significant difference in the rate of good clinical outcome defined as mRs of 0-2 or return to baseline (47.4 vs 61.1%, p value=0.18); rate of any HI (29.8% vs. 27.8%, p value=0.84) and sICH(5.3% vs 0%, p value=0.24) between the two groups (drip vs. no drip). When comparing the NCR to CLV groups, median ROBP was significantly shorter in the CLV group, 5min (IQR 0.75-7) vs. 17min (IQR 6-35), p value= 0.003; and total duration of time outside the pre-specified BP range was 37.5 min (IQR 19-120) vs. 118 min (57-227) consecutively, p value=0.045. HT rates (14.3% vs. 34.9%, p value=0.19), sICH rates (0 vs. 7%, p value=0.57), and rate of good clinical outcome (64.3% vs. 41.9%, p value=0.22) were similar between the two groups (CLV vs. NCR). In a Multivariate analysis, after adjusting for age, gender, IV tPA administration, drip used and time out of range; NIHSS (OR 0.8, CI 0.70-0.91, p=0.0008) and ROBP (OR=1.05, CI 1.0-1.1, p value=0.032) were independent predictors of good clinical outcome. Conclusion CLV achieved faster ROBP time and better BP control after MT. Further prospective studies are needed.

Research paper thumbnail of O-022 White matter survival within and around the hematoma: quantification by MRI in patients with intracerebral hemorrhage

Oral abstracts, 2021

scans; and 4. Motion compensation post-processing algorithm technology. Methods Patients with AIS... more scans; and 4. Motion compensation post-processing algorithm technology. Methods Patients with AIS who received endovascular mechanical thrombectomy were prospectively included in this monocentric study (n=105). Study 1: Image quality of non-contrast circular CB-CT scans were analyzed using 2 quantitative and 6 qualitative measures and were compared to CT. Study 2: 6 types of image artifacts were compared between circular and dual-axis CB-CT scans. Study 3: Clot detection, ischemic core and collateral blood supply was assessed on CB-CT Perfusion imaging and compared to baseline CT and DSA imaging. Study 4: Motion artifacts were assessed on all scans before and after post-processed using a motion artifact correction algorithm. Results Study 1: Newer non-contrast CB-CT circular scans had higher mean contrast-to-noise ratio and lower mean image noise compared to older generation protocols. The largest image quality improvements included grey/white matter differentiation (59% improvement), and reduction of image noise and artefacts (63% & 50% improvement, respectively). Study 2: Dual-axis CB-CT scans had significantly improved beam hardening and cone-beam artifacts compared to circular scans. Study 3: CB-CT stroke perfusion imaging software accurately demonstrates vessel patency, ischemic core, and collateral blood supply. Study 4: 51% of all AIS CB-CT scans had motion artifacts, of which 91% improved after post-processing with our motion correction algorithm. Overall 76% of the scans were sufficient for clinical decision making prior to correction, which improved to 93% after post processing with our algorithm. Conclusions The latest generation of CB-CT scans & technology allow for exclusion of haemorrhages, stroke core definition and demonstration of brain perfusion and collaterals. These improvements suggest that CB-CT is acceptable for emergency stroke imaging assessment before mechanical thrombectomy, which may reduce door-to-groin puncture times and improve patient outcomes.

Research paper thumbnail of Radiotherapy (RT) Dose-intensification (DI) Using Intensity-modulated RT (IMRT) versus Standard-dose (SD) RT with Temozolomide (TMZ) in Newly Diagnosed Glioblastoma (GBM): Preliminary Results of NRG Oncology BN001

International Journal of Radiation Oncology*Biology*Physics, 2020

of upfront SRS remains controversial because of lack of randomized evidence. Materials/Methods: I... more of upfront SRS remains controversial because of lack of randomized evidence. Materials/Methods: In this phase III randomized controlled trial (NCT01592968), adult patients with 4-15 untreated non-melanoma BMs were stratified by histology, number of lesions, baseline Hopkins Verbal Learning Test-Revised Total Recall (HVLT-R TR) score, extracranial disease, KPS, and age, and randomly assigned to SRS or WBRT. Memantine was encouraged in the WBRT arm after publication of RTOG 0614. Prior SRS to 1-3 BMs with at least 3 months (mos) interval was allowed. Test of neurocognitive function (NCF) were completed at baseline and longitudinally including tests of learning and memory (HVLT-R), verbal fluency (Controlled Oral Word Association (COWA), and processing speed and executive function (Trail Making Test Parts A [TMTA] and B [TMTB]). Primary endpoints were HVLT-R TR and local control (LC) at 4 mos. Secondary endpoints included additional NCF tests, overall survival (OS), distant brain failure, toxicity, and time to systemic therapy. The trial was terminated early due to slow accrual. Results: Between 09/2012 and 09/2019, 72 patients were randomized to SRS (n Z 36) or WBRT (n Z 36) with an estimated median follow-up time of 6.6 mos (range 0.2-69.8). Median number of BMs at enrollment was 8. Thirty-one patients were evaluable for HVLT-R TR at 4 mos. In the WBRT arm, 62% of patients received memantine. In the primary endpoint analysis, relative to baseline, the 4 mo HVLT-R TR standardized z-score increased by +0.21 (standard error [SE] 0.27) for SRS-treated patients and declined by-0.74 (SE 0.36) for WBRT-treated patients (p Z 0.041). Based on the Clinical Trial Battery Composite (the mean z-score for the HVLT-R, COWA, TMT), at 4 mos the NCF of patients in the SRS arm improved on average +0.23 (SE 0.14) and the NCF of patients in the WBRT arm declined on average-0.73 (SE 0.35), p Z 0.008. Median OS time was 10.4 mos for SRS and 8.4 mos for WBRT (p Z 0.45). Preliminary analyses of LC at 4 mos demonstrated 100% LC rate for SRS and 95.5% for WBRT (p Z 0.53), and median time to distant brain failure (DBF) was 4.3 mos for SRS vs.18.1 mos for WBRT (p Z 0.09). LC and DBF results are being independently confirmed by the trial radiologist presently. Conclusion: In non-melanoma patients with 4-15 brain metastases, SRS was associated with reduced risk of neurocognitive deterioration relative to WBRT without compromising OS. These results provide level 1 evidence to support the use of SRS in patients with 4-15 brain metastases amenable to SRS.

Research paper thumbnail of O-006 Histotripsy for intracerebral hemorrhage in a porcine model

Oral Abstracts, 2020

applicable in the US. This study prospectively validates the RACE scale as administered by US-bas... more applicable in the US. This study prospectively validates the RACE scale as administered by US-based EMS personnel in the pre-hospital setting and we compare our results to the originally published results. Methods 232 adult patients suspected of having a stroke by EMS and transported to a participating comprehensive stroke center had the RACE scale administered prospectively and recorded in a secure web-based database. Admission NIHSS score and final diagnosis were recorded. Cerebrovascular imaging studies (CTA, MRA or DSA) were reviewed by a blinded, independent Neuroradiologist to determine LVO diagnosis. We used SAS and c-statistics to create receiver operating characteristic (ROC) curves to determine the area under the curve (AUC) and optimal cut point (CP) scores for the RACE scale. We also calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy for the optimal CP score. Results Our analysis of the predictive capability of the RACE scale showed similar predictive capacities for radiographicallyconfirmed LVO in patients prospectively tested in the US as compared to the original Spanish RACE scale population. The best CP score value predictive of LVO in our US-RACE study was determined to be !6, compared to the original Spanish study which was !5 (table 1). The overall prevalence of LVO as defined in our study was 13.4%, compared to a prevalence of 21.3% for the original paper's definition of LVO. Conclusion This is the first prospective validation of the RACE scale performed in the US. These results demonstrate that the RACE scale retains the previously published predictive value in both the US and Spain in accurately identifying LVO stroke in a prehospital setting by EMS.

Research paper thumbnail of Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives

European Radiology, 2017

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic in... more For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials Contribution of NIST-not subject to copyright in the US * N. M. deSouza

Research paper thumbnail of A Flexible Spline Model of the Spin Echo with Applications to Estimation of the Spin-Spin Relaxation Time

Journal of Magnetic Resonance, Series A, 1994

Research paper thumbnail of Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis

British journal of cancer, Jan 18, 2017

Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadj... more Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC. Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest ...

Research paper thumbnail of TU-C-12A-08: Thermally-Stabilized Isotropic Diffusion Phantom for Multisite Assessment of Apparent Diffusion Coefficient Reproducibilty

Medical Physics, 2014

PURPOSE To construct an appropriate phantom for quality control use in diffusion-weighted imaging... more PURPOSE To construct an appropriate phantom for quality control use in diffusion-weighted imaging (DWI), to establish ground truth for measurement of apparent diffusion coefficient (ADC) and to characterize measurement linearity across a relevant physiological range of ADC. METHODS Aqueous solutions containing the polymer polyvinylpyrrolidone (PVP) were mixed at concentrations of 0, 10, 20, 30, 40 and 50% by mass PVP. These solutions were placed in 20 mL vials, arranged in concentric inner and outer circles, with a central water vial, and were fixed in a spherical phantom with a diameter of 194 mm, designed to fit into commercially-available MRI head coils. Two prototype phantoms were constructed, and underwent inter-site comparison in the US and EU. The phantoms were filled with an ice-water bath to ensure stable temperature; 0 °C temperature was verified by use of a thermocouple before and after scans. The phantoms were scanned using b-values of 0, 500 and 900 s/mm2 at several sites, using coronal and/or axial orientations and scan planes. RESULTS ADC values ranged from 0.12 to 1.12 × 10-3 mm2 /s, and exhibited a high degree of reproducibility across different scanners and imaging sites (coefficient of variations (CoV) ranged from 1.1 to 2.2% for 0 to 40% PVP, with 50% PVP at 11.3%). Little difference in ADCs was seen between inner and outer ring vials of the same PVP concentration (average CoV< 5% across vials, 10.3% for 50% PVP). CONCLUSION The range of ADCs covers a relevant physiological range, most notably in brain white matter. The ADCs of water vials were in excellent agreement with literature values of the diffusion coefficient of water at 0 °C (1.1 × 10-3 mm2 /s). The phantom provides a much needed quality control tool for DWI, and provides ground truth with the diffusion coefficient of water at 0 °C.

Research paper thumbnail of 2134: Incorporating Individualized Target Motion and Deformation in IMRT Planning for Unresectable Pancreatic Cancer: Dosimetric Implications

medication or any grade 3-4 toxicity. SPSS software was used to calculate Kaplan-Meier survival e... more medication or any grade 3-4 toxicity. SPSS software was used to calculate Kaplan-Meier survival estimates and 2-tailed t-tests for comparisons. Results: Gastrointestinal toxicity grade 3-4 was recorded in 4.2 % of patients who received 1.8 Gy vs. 19.4% for patients who received 2.4 Gy fractions (pϭ0.05). 3/24 patients (12.5%) that received 1.8Gy fractions required a treatment break compared to 14/36 (38.8%) that received 2.4 Gy fractions (pϭ0.02). Median survival was 16.4 months 95% CI [10.3,22.4] for patients with LA disease treated with standard fractionation vs. 11.1 months 95%CI [8.2,13.9] for hypofractionation. For patients treated after Whipple resection with hypofractionation, median survival was 17.2 months and has not yet been reached for patients treated with standard fractionation. Conclusions: In comparison with hypofractionated chemoradiation with concurrent full dose gemcitabine for pancreatic cancer, standard fractionation is associated with significantly less grade III-IV gastrointestinal toxicity and fewer treatment breaks. These results suggest that dose escalation studies using standard fractions may be advantageous for pancreatic cancer.

Research paper thumbnail of 1108: Proton Magnetic Spectroscopy (1H-MRSI) of Early Versus Late Delayed Radiation-Induced Effect of Normal White Matter in Malignant Glioma Patients

Research paper thumbnail of Phase-Based Imaging of Magnetically Tagged Cells

Research paper thumbnail of TH-E-ValB-06: Quantitative Characterization of Tumor Vascular Dysfunction in High-Grade Gliomas Prior to and During Radiotherapy

Medical Physics, 2006

Introduction: Vascular properties within and adjacent to tumors may not be distinguishable by cer... more Introduction: Vascular properties within and adjacent to tumors may not be distinguishable by cerebral blood flow [CBF] or cerebral blood volume [CBV] alone, since the rates of CBV change may not be proportional in magnitude to CBF change. Hence, the empirical and physiological relationships between CBF and CBV were examined to estimate vasculature‐specific hemodynamiccharacteristics in high‐grade gliomas. Methods: Twenty patients with gliomas were studied with dynamic contrast‐enhanced T2* MRI [DCE‐MRI] before and during radiotherapy [RT]. CBF and CBV were calculated from DCE‐MRI and the relationships between the two were evaluated using two different metrics: The physiological measure of Mean Transit Time [MTT]=CBV/CBF; and, Empirical fitting of CBV and CBF using the power law, expressed as CBV=Constant*(CBF)β. Three tissue types were assessed, Gd‐enhanced tumor volume [GdTV], non‐enhancing abnormal tissue located beyond GdTV but within the abnormal hyperintense volume on FLAIR images [NEV], and normal tissue in hemisphere contralateral to tumor[CNT]. Effects of tissue types, CBV magnitudes (low[L], medium[M] and high[H] CBV), before and during RT, on MTT and β were analyzed by factorial ANOVA. Results: Both, MTT and β were significantly different (p<0.009) among the three tissue types. MTT increased from CNT(=1.60s) to NEV(=1.93s) to GdTV(=2.28s) (<0.0005). The power exponent β was significantly greater in GdTV(=1.079) and NEV(=1.070) than CNT(=1.025), but β in NEV and GdTV were not significantly different from each other. β increased with increasing CBV magnitude. There was a significant decrease in MTT and a significant increase in β in tumor (GdTV) and peritumoral (NEV) tissue during RT compared with pre‐RT values. Conclusions: β was strongly dependent on CBV magnitude and MTT on tissue type. Progressive abnormalities in functional characteristics of the vascular bed were noted, with significant disorder in tumor, but mild abnormality in peritumoral tissue. Early vascular response to radiation was first observed in functional rather than structural properties.

Research paper thumbnail of TH-D-AUD C-01: Early Blood-Brain-Barrier Disruption in Response to RT as a Biomarker for Neurotoxicity

Medical Physics, 2008

Purpose: Studies of neurocognitive dysfunction after radiation in animals suggest that vascular i... more Purpose: Studies of neurocognitive dysfunction after radiation in animals suggest that vascular injury plays a key role. We hypothesized that blood‐brain‐barrier (BBB) disruption in normal appearing cerebral tissue of patients early in the course of fractionated radiation therapy (RT) is a biomarker for delayed neurocognitive dysfunction. Method and Materials: Ten patients with low‐grade glioma, or suprasellar lesion and underwent 3D conformal cranial RT (28–33 fx of 1.8 Gy) participated in a prospective MRI study. Dynamic‐contrast enhanced (DEC) MRI was acquired before, at week 3 and week 6 during the course of, and at 1, 6 and 18 months after the completion of RT. Using the modified Toft model, the contrast transfer constant (K) from the intravascular space to the extravascular extracellular space was estimated. A battery of standardized neuropsychological tests was performed at the same times as the pre‐ and post‐RT MRI. The relationship between the temporal changes in K and the dosimetric parameters was analyzed by a linear mixed model. Correlations between the changes in K and early delayed changes in the neurocognitve functions were analyzed by linear regression.Results: The K values increased significantly in normal appearing tissue regions that received >40 Gy at week 6 during RT (p<0.05), suggesting BBB opening. The elevated K values decreased gradually after RT. The changes in K both during and after RT were significantly correlated with the doses received at the time but the significance decreased from p = 0.0001 at week 3 during RT to 0.03 at 6 months after RT. The changes in K of left frontal lobe at week 3 during RT were significantly negatively correlated with the changes in verbal learning scores at 6 months after RT (p<0.02). Conclusion: Our data suggest early BBB disruption could be a biomarker for delayed neurocognitve function deterioration. Supported by NIHP01CA59827 and R21CA11369901.