Parametric Modeling of the Brain Vascular System and its Application in Dynamic Contrast-Enhanced Imaging Studies.

Dynamic Contrast-Enhanced Imaging (DCE) is one of the main tools for in vivo measurement of vascular properties of pathologies such as brain tumors. In DCE imaging, one of the key components for estimation of vascular perfusion and permeability parameters using Pharmacokinetic models is the Arterial Input Function (AIF). To measure these parameters more accurately, there have been approaches for estimating the AIF profile at the capillary level; however, a practical and realistic estimate is still missing. As a solution, we have developed a model of the brain vascular system, based on laws of fluid dynamics and vascular morphology, to address dispersion and delay of the contrast agent (CA) concentration profile at different levels of the brain vascular tree. Using this model, we introduced a transfer function that can describe changes of the AIF profile along a vascular pathway, from a major artery to the capillary bed. Our simulations and also testing this model on DCE Imaging data of the human brain, all showed that our model can give a realistic estimation of the CA concentration profile, at all levels of the vascular tree in the brain. In the next step, we extended our model to address vascular leakage as well. Using this extended vascular (EV) model, we are able to decompose the tissue response signal in DCE images to its intravascular and extravascular components. This feature has provided us with an excellent tool that can lead to relatively unbiased measurements of perfusion and permeability parameters, especially in areas with vascular leakage. We tested this on DCE-CT and DCE-MR images and compared the performance of our model to conventional methods. Also, using a simulation study, we measured the levels of overestimation and underestimation of the permeability parameters using conventional processing methods and demonstrated the superior performance of the EV model for more accurate estimation of these parameters. Overall, the results show that the EV model can provide a platform for better understanding of the role of the AIF in DCE studies as well as estimation of AIF for more accurate measurement of perfusion and permeability parameters in clinical studies.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107177/1/siamak_1.pd

Performance of deep learning synthetic CTs for MR-only brain radiation therapy

PURPOSE: To evaluate the dosimetric and image-guided radiation therapy (IGRT) performance of a novel generative adversarial network (GAN) generated synthetic CT (synCT) in the brain and compare its performance for clinical use including conventional brain radiotherapy, cranial stereotactic radiosurgery (SRS), planar, and volumetric IGRT. METHODS AND MATERIALS: SynCT images for 12 brain cancer patients (6 SRS, 6 conventional) were generated from T1-weighted postgadolinium magnetic resonance (MR) images by applying a GAN model with a residual network (ResNet) generator and a convolutional neural network (CNN) with 5 convolutional layers as the discriminator that classified input images as real or synthetic. Following rigid registration, clinical structures and treatment plans derived from simulation CT (simCT) images were transferred to synCTs. Dose was recalculated for 15 simCT/synCT plan pairs using fixed monitor units. Two-dimensional (2D) gamma analysis (2%/2 mm, 1%/1 mm) was performed to compare dose distributions at isocenter. Dose-volume histogram (DVH) metrics (D(95%) , D(99%) , D(0.2cc,) and D(0.035cc) ) were assessed for the targets and organ at risks (OARs). IGRT performance was evaluated via volumetric registration between cone beam CT (CBCT) to synCT/simCT and planar registration between KV images to synCT/simCT digital reconstructed radiographs (DRRs). RESULTS: Average gamma passing rates at 1%/1mm and 2%/2mm were 99.0 ± 1.5% and 99.9 ± 0.2%, respectively. Excellent agreement in DVH metrics was observed (mean difference ≤0.10 ± 0.04 Gy for targets, 0.13 ± 0.04 Gy for OARs). The population averaged mean difference in CBCT-synCT registrations were \u3c0.2 mm and 0.1 degree different from simCT-based registrations. The mean difference between kV-synCT DRR and kV-simCT DRR registrations was \u3c0.5 mm with no statistically significant differences observed (P \u3e 0.05). An outlier with a large resection cavity exhibited the worst-case scenario. CONCLUSION: Brain GAN synCTs demonstrated excellent performance for dosimetric and IGRT endpoints, offering potential use in high precision brain cancer therapy

Optimization of a novel large field of view distortion phantom for MR-only treatment planning

PURPOSE: MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. METHOD AND MATERIALS: To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform. RESULTS: All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate \u3e 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer\u27s plugin framework and results agreed with the literature. CONCLUSION: The design and implementation of a modular, extendable distortion phantom was optimized for several bore configurations. The phantom and analysis software will be available for multi-institutional collaborations and cross-validation trials to support MR-only planning

Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (

Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE‐MRI nested model selection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109323/1/jmri24469.pd

Geometric and dosimetric impact of anatomical changes for MR-only radiation therapy for the prostate

PURPOSE: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions. MATERIALS AND METHODS: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state. RESULTS: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%). CONCLUSIONS: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols

MRI of Neuronal Recovery After Low-Dose Methamphetamine Treatment of Traumatic Brain Injury in Rats

We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day prior to TBI, and at 1 and 3 days post TBI, and then weekly for 6 weeks. The lesion volumes of TBI damaged cerebral tissue were demarcated by elevated values in T2 maps and were histologically identified by hematoxylin and eosin (H&E) staining. The fractional anisotropy (FA) values within regions-of-interest (ROI) were measured in FA maps deduced from DTI, and were directly compared with Bielschowsky’s silver and Luxol fast blue (BLFB) immunohistological staining. No therapeutic effect on lesion volumes was detected during 6 weeks after TBI. However, treatment significantly increased FA values in the recovery ROI compared with the control group at 5 and 6 weeks after TBI. Myelinated axons histologically measured using BLFB were significantly increased (p,0.001) in the treated group (25.8461.41%) compared with the control group (17.0562.95%). Significant correlations were detected between FA and BLFB measures in the recovery ROI (R = 0.54, p,0.02). Methamphetamine treatment significantly reduced modified neurological severity scores from 2 to 6 weeks (p,0.05) and foot-fault errors from 3 days to 6 weeks (p,0.05) after TBI. Thus, the FA data suggest that methamphetamine treatment improves white matter reorganization from 5 to 6 weeks after TBI in rats compared with saline treatment, which may contribute to the observed functional recovery

Model selection for DCE‐T1 studies in glioblastoma

Dynamic contrast enhanced T 1 ‐weighted MRI using the contrast agent gadopentetate dimeglumine (Gd‐DTPA) was performed on 10 patients with glioblastoma. Nested models with as many as three parameters were used to estimate plasma volume or plasma volume and forward vascular transfer constant ( K trans ) and the reverse vascular transfer constant ( k ep ). These constituted models 1, 2, and 3, respectively. Model 1 predominated in normal nonleaky brain tissue, showing little or no leakage of contrast agent. Model 3 predominated in regions associated with aggressive portions of the tumor, and model 2 bordered model 3 regions, showing leakage at reduced rates. In the patient sample, v p was about four times that of white matter in the enhancing part of the tumor. K trans varied by a factor of 10 between the model 2 (1.9 ↔ 10 −3 min −1 ) and model 3 regions (1.9 ↔ 10 −2 min −1 ). The mean calculated interstitial space (model 3) was 5.5%. In model 3 regions, excellent curve fits were obtained to summarize concentration‐time data (mean R 2 = 0.99). We conclude that the three parameters of the standard model are sufficient to fit dynamic contrast enhanced T 1 data in glioblastoma under the conditions of the experiment. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91323/1/23211_ftp.pd

Novel phantom validation of susceptibility-related distortions.

Purpose: MR-only treatment planning and MR-IGRT require high fidelity anatomical patient models for precise radiation therapy. Computer simulations have shown that local susceptibility changes at tissue/air interfaces increase with increased field strength and size of the inhomogeneity. However, it has been challenging to validate these effects. This work evaluates the potential of using a novel pelvic phantom with variable bladder and air-filled rectal balloon inserts to benchmark susceptibility-related distortions. Methods: A novel pelvic end-to-end (PETE) MR-compatible phantom with variable anatomies was imaged on a 1.0 T MR-Simulator and 0.35 T MR-Linac. The phantom consists of anthropomorphic pelvic bones and two fillable silicone balloons designed to mimic the bladder and rectum. For all experiments, the fluid-filled bladder volume was kept constant at 250 CC while rectal air was varied at 30 CC, 90 CC and 150 CC. Dual-echo gradientrecalled echo images were acquired on both systems. Maps of the phase differences were reconstructed after complex division of the complex data from the two echoes. Distortion maps were then generated using magnet-specific image acquisition parameters. Results: Distortion maps showed an increase in distortion magnitude and distortion ranges in surrounding tissues with increased rectal air. In a 2 cm ring around the 150 CC rectum, susceptibilityinduced distortions were -0.02 ± 0.04 (range: -0.26-0.15) and -0.02 ± 0.05 (range: -0.44-0.30) for the 1.0 T and 0.35 T, respectively. At 0.35 T, peak distortions at the rectal boundary decayed radially to half its value within 16 mm and 14 mm for the 150 CC and 90 CC rectal gas volumes, respectively. At 1 T, these ranges were 14 mm and 12 mm, respectively. Conclusion: Our phantom mimicking varied rectal conditions allowed quantification of local susceptibility distortions. While distortions increased with increased air volume, the distortion measured for low fields was \u3c1mm. Evaluation in higher field strengths is warranted. Future applications of the phantom include benchmarking distortion correction schemes

Comparison of Two Methods for Patient Specific Distortion Corrections for MR Only Treatment Planning

Purpose: While MRI-only treatment planning is becoming more widespread, a robust clinical solution for patient-specific distortion corrections is not currently available. This work explores an alternative approach for B0- mapping estimated from mDixon, often acquired for MR-only planning, compared to a dedicated dual-echo gradient-recalled echo (GRE) sequence, with the overarching goal of developing an efficient and robust approach for patient-specific distortion correction maps. Methods: Healthy volunteers were imaged in the pelvis and head and neck (H&N) regions at 1.5T and 3T. B0 field maps were generated with two approaches: (1) conventional: dualecho GRE (using two in-phase echo times) and (2) experimental: mDIXON using much shorter echo times. Additionally, the impact of acquisition resolution was evaluated for 1.7 9 1.7 9 5 mm (low resolution, LR) vs. 1.2 9 1.2 9 2.4 mm (high resolution, HR) in H&N. Distortion maps were generated from B0 field maps based on bandwidth and acquisition pixel size and compared between approaches. Results: In H&N, mDIXON revealed similar distortion magnitudes between field strengths (\u3c0.5 mm). Distortions were higher near ear canals (∼1 mm), sinuses (∼1 mm) and dental fillings (\u3e1 mm). HR B0 maps were more sensitive at interfaces than LR, although LR was suitable given its overall accuracy in bulk voxels and shorter acquisition time (40% of HR). LR conventional GRE was well-approximated by mDIXON: 96% (1.5T) and 99% (3T) of voxels estimated by mDixon differed from their GRE maps by \u3c0.5 mm. In the pelvis, 99% of GRE distortion voxels and 100% of mDixon distortion voxels were within ±0.3 mm. Differences between techniques occurred near regions with high spatial variation and with phase unwrapping errors. Conclusion: mDIXON closely approximated GRE for patient-specific distortion assessment. Slight differences observed near tissue interfaces require further assessment to determine geometric and dosimetric impact. mDIXON-derived B0 maps may be advantageous for integration into in-line processing without requiring additional sequences