Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model

AbstractTo analyze radiation induced changes in Hounsfield units and determine their correlation with changes in perfusion and ventilation. Additionally, to compare the post-RT changes in human subjects to those measured in a swine model used to quantify perfusion changes and validate their use as a preclinical model. A cohort of 5 Wisconsin Miniature Swine (WMS) were studied. Additionally, 19 human subjects were recruited as part of an IRB approved clinical trial studying functional avoidance radiation therapy for lung cancer and were treated with SBRT. Imaging (a contrast enhanced dynamic perfusion CT in the swine and 4DCT in the humans) was performed prior to and post-RT. Jacobian elasticity maps were calculated on all 4DCT images. Contours were created from the isodose lines to discretize analysis into 10 Gy dose bins. B-spline deformable image registration allowed for voxel-by-voxel comparative analysis in these contours between timepoints. The WMS underwent a research course of 60 Gy in 5 fractions delivered locally to a target in the lung using an MRI-LINAC system. In the WMS subjects, the dose-bin contours were copied onto the contralateral lung, which received < 5 Gy for comparison. Changes in HU and changes in Jacobian were analyzed in these contours. Statistically significant (p < 0.05) changes in the mean HU value post-RT compared to pre-RT were observed in both the human and WMS groups at all timepoints analyzed. The HU increased linearly with dose for both groups. Strong linear correlation was observed between the changes seen in the swine and humans (Pearson coefficient > 0.97, p < 0.05) at all timepoints. Changes seen in the swine closely modeled the changes seen in the humans at 12 months post RT (slope = 0.95). Jacobian analysis showed between 30 and 60% of voxels were damaged post-RT. Perfusion analysis in the swine showed a statistically significant (p < 0.05) reduction in contrast inside the vasculature 3 months post-RT compared to pre-RT. The increases in contrast outside the vasculature was strongly correlated (Pearson Correlation 0.88) with the reduction in HU inside the vasculature but were not correlated with the changes in Jacobians. Radiation induces changes in pulmonary anatomy at 3 months post-RT, with a strong linear correlation with dose. The change in HU seen in the non-vessel lung parenchyma suggests this metric is a potential biomarker for change in perfusion. Finally, this work suggests that the WMS swine model is a promising pre-clinical model for analyzing radiation-induced changes in humans and poses several benefits over conventional swine models.

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Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model

10.21203/rs.3.rs-257237/v1 ◽

2021 ◽

Author(s):

Antonia E. Wuschner ◽

Eric M. Wallat ◽

Mattison J. Flakus ◽

Dhanansayan Shanmuganayagam ◽

Jennifer Meudt ◽

...

Keyword(s):

Linear Correlation ◽

Ct Perfusion ◽

Human Subjects ◽

Pearson Correlation ◽

Preclinical Model ◽

Swine Model ◽

Potential Biomarker ◽

Strong Linear Correlation ◽

Radiation Induced ◽

Induced Changes

Abstract Purpose: To analyze radiation induced changes in Hounsfield units and determine their correlation with changes in perfusion and ventilation. Additionally, to compare the post-RT changes in human subjects to those measured in a swine model used to quantify perfusion changes, and validate their use as a preclinical model. Methods: A cohort of 5 Wisconsin Miniature Swine (WMS™) were studied. Additionally, 19 human subjects were recruited as part of an IRB approved clinical trial studying functional avoidance radiation therapy for lung cancer and were treated with SBRT. Imaging (a contrast enhanced dynamic perfusion CT in the swine and 4DCT in the humans) was performed prior to and post-RT. Jacobian elasticity maps were calculated on all 4DCT images. Contours were created from the isodose lines to discretize analysis into 10 Gy dose bins. B-spline deformable image registration allowed for voxel-by-voxel comparative analysis in these contours between timepoints. The WMS™ underwent a research course of 60 Gy in 5 fractions delivered locally to a target in the lung using an MRI-LINAC system. In the WMS™ subjects, the dose-bin contours were copied onto the contralateral lung, which received < 5 Gy for comparison. Changes in HU and changes in Jacobian were analyzed in these contours.Results: Statistically significant (p < 0.05) changes in the mean HU value post-RT compared to pre-RT were observed in both the human and WMS™ groups at all timepoints analyzed. The HU increased linearly with dose for both groups. Strong linear correlation was observed between the changes seen in the swine and humans (Pearson coefficient > 0.97, p< 0.05) at all timepoints. Changes seen in the swine closely modeled the changes seen in the humans at 12 months post RT (slope=0.95). Jacobian analysis showed between 30-60% of voxels were damaged post-RT. Perfusion analysis in the swine showed a statistically significant (p < 0.05) reduction in contrast inside the vasculature 3 months post-RT compared to pre-RT. The increases in contrast outside the vasculature was strongly correlated (Pearson Correlation 0.88) with the reduction in HU inside the vasculature but were not correlated with the changes in Jacobians. Conclusions: Radiation induces changes in pulmonary anatomy at 3 months post-RT, with a strong linear correlation with dose. The change in HU seen in the non-vessel lung parenchyma suggests this metric is a potential biomarker for change in perfusion. Finally, this work suggests that the WMS™ swine model is a promising pre-clinical model for analyzing radiation-induced changes in humans and poses several benefits over conventional swine models.

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HOUT-07. ASSOCIATION BETWEEN BASELINE BODY MASS INDEX (BMI) AND OUTCOMES FOR PATIENTS WITH GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.472 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi113-vi113

Author(s):

Jessica Chew ◽

Olivier Morin ◽

Steve Braunstein

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Linear Correlation ◽

Pearson Correlation ◽

Baseline Body Mass Index ◽

Single Institution ◽

Cox Proportional Hazard ◽

Significant Linear Correlation ◽

Strong Linear Correlation

Abstract OBJECTIVES This single institution retrospective study aims to evaluate the association between body mass index (BMI) and survival in glioblastoma (GBM). METHODS Patients were identified using a single institution cancer registry. Baseline height and weight were obtained at first clinical visit after diagnosis. Inclusion criteria were GBM diagnosis after 1999 with available height and weight data. Follow up was through July 2018. RESULTS 779 patients were included who had available BMI data. Median age was 58 (IQR 48–66). 38% of patients were female and 62% were male. Median overall survival (OS) was 1.34 years (IQR 0.78–2.12) and median BMI was 26.01 (IQR 23.3–29.1). There was no strong linear correlation between OS and BMI using Pearson correlation (r=0.045). Patients with higher BMI had significantly improved OS when comparing the top 50% to bottom 50% (2.20 vs 1.89 years, p=0.03) and top 25% to bottom 25% (2.25 vs 1.84 years, p=0.03). When comparing patients classified as overweight or obese (BMI >/= 25) to those within normal range or below (BMI < 25), there was a trend towards increased OS (2.14 vs 1.90 years, p=0.075). There was no significant trend for BMI when comparing patients with higher OS with lower OS. There was also no significance for BMI on Cox proportional hazard multivariate analysis. CONCLUSIONS There was no significant linear correlation between BMI and survival for GBM patients, although there appears to be statistically significant improved survival benefit for patients with higher BMI compared to patients with lower BMI. Further investigation is warranted to explore this finding and if BMI could be used as a potential prognostic marker for GBM.

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sRAGE as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0035-1547693 ◽

2015 ◽

Vol 122 (03) ◽

Author(s):

I Hagen ◽

D Schulte ◽

N Mueller ◽

J Martinsen ◽

K Türk ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Human Subjects ◽

Very Low Calorie Diet ◽

Low Calorie ◽

Low Calorie Diet ◽

Potential Biomarker ◽

Calorie Diet ◽

Predict Weight Loss ◽

Obese Human

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Space Radiation-Induced Alterations in the Hippocampal Ubiquitin-Proteome System

International Journal of Molecular Sciences ◽

10.3390/ijms22147713 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7713

Author(s):

Alyssa Tidmore ◽

Sucharita M. Dutta ◽

Arriyam S. Fesshaye ◽

William K. Russell ◽

Vania D. Duncan ◽

...

Keyword(s):

Spatial Memory ◽

Memory Performance ◽

Space Radiation ◽

Label Free ◽

Proteomic Profiling ◽

Neurocognitive Deficits ◽

Male Wistar Rats ◽

Radiation Induced ◽

Induced Changes

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.

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Impact of [18F]FDG-PET and [18F]FLT-PET-Parameters in Patients with Suspected Relapse of Irradiated Lung Cancer

Diagnostics ◽

10.3390/diagnostics11020279 ◽

2021 ◽

Vol 11 (2) ◽

pp. 279

Author(s):

Tine N. Christensen ◽

Seppo W. Langer ◽

Gitte Persson ◽

Klaus Richter Larsen ◽

Annemarie G. Amtoft ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Fdg Pet ◽

Tumor Volume ◽

High Dose ◽

Flt Pet ◽

Pet Ct ◽

Radiation Induced ◽

Fdg Pet Ct ◽

Induced Changes

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

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Should CD138 Immunohistochemistry be Standard Recommended Practice for Bone Marrow Evaluation of Plasma Cell Neoplasms?

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.241 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S110-S110

Author(s):

A Vijayanarayanan ◽

K Inamdar ◽

M Menon ◽

P Kuriakose

Keyword(s):

Bone Marrow ◽

Plasma Cell ◽

Linear Correlation ◽

Plasma Cells ◽

Pearson Correlation ◽

Protein Electrophoresis ◽

Pearson Correlation Coefficient ◽

Cell Percentage ◽

Significant Linear Correlation ◽

Plasma Cell Neoplasms

Abstract Introduction/Objective Myeloma diagnosis by a pathologist requires 10% plasma cells (PC) or a biopsy proven plasmacytoma in addition to myeloma defining events. PC% > 60% is a biomarker of malignancy under this definition. WHO allows for assesment of plasma cell percentage either by aspirate count or by CD138 immunohistochemistry (IHC). There is lack of consensus on aspirate smear adequacy for PC% estimation. Uneven distribution of plasma cells, hemodilution and/or patchy infiltration can lead to gross underestimation. We compared PC% by aspirate count and CD138 IHC and established corelation with serum protein electrophoresis (SPEP) values. Methods 67 myeloma cases were included after excluding cases with suboptimal or inadequate aspirate smears. Two hematopathologists evaluated the diagnostic marrow (therapy naive) for PC% by aspirate count and CD138 IHC on biopsy/clot section. Corresponding SPEP and Free light chain (FLC) values were obtained. Correlation coefficent was calculated using Pearson correlation coefficient (GraphPad Prism). Results The Ig subtypes included IgG (41/67) and IgA (17/67). 12 cases had available FLC values. Both average and median PC% by CD138 IHC was considerably higher (50%, 52%) compared to aspirate count (29%, 21%). However, PC% by aspirate smear count and CD138 IHC demonstrated a significant linear correlation (r=0.71, p60% by CD138 (and not by aspirate count). Conclusion CD138 IHC based PC% is consistently higher, nevertheless, statistically significant linear corelation is observed between aspirate count PC% and CD138 IHC. A significant linear correlation is observed between CD138 IHC and SPEP (IgG and IgA), however, no such correlation is observed with aspirate count. More cases were diagnosed as myeloma (11%) and higher propotion of cases (35%) had biomarker of malignancy i.e. PC% >60% by CD138 IHC. Based on these findings, we propose estimation of PC% by CD138 immunostain be a recommended standard practice for better clinicopathologic and biologic correlation.

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