Medicine and Health Sciences Commons^™

Noninvasive Quantification Of Alveolar Morphometry In Elderly Never- And Ex-Smokers, Gregory A Paulin, Alexei Ouriadov, Eric Lessard, Khadija Sheikh, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Diffusion-weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized (3)He MRI estimates of the alveolar dimensions in 38 healthy elderly never-smokers (73 ± 6 years, 15 males) and 21 elderly ex-smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex-smoker and never-smoker subgroups were significantly different for FEV1/FVC (P = 0.0001) and DLCO (P = 0.009); while ex-smokers …

Copd: Do Imaging Measurements Of Emphysema And Airway Disease Explain Symptoms And Exercise Capacity?, Miranda Kirby, Damien Pike, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease.

MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and …

Serum Vitamin D Status Is Associated With The Presence But Not The Severity Of Primary Open Angle Glaucoma., Aurélien Goncalves, Dan Milea, Philippe Gohier, Ghislaine Jallet, Stéphanie Leruez, Mani Baskaran, Tin Aung, Cédric Annweiler

Medical Biophysics Publications

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults.

STUDY DESIGN: Case-control study.

MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1±8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0±7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence tomography. Severe POAG was defined as Humphrey visual field …

Ventilation Heterogeneity In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Fumin Guo, David G Mccormack, Grace Parraga

Medical Biophysics Publications

RATIONALE AND OBJECTIVES: Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP).

MATERIALS AND METHODS: Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤-950 HU, RA950) and …

Survival Prediction In High-Grade Gliomas Using Ct Perfusion Imaging., Timothy Pok Chi Yeung, Yong Wang, Wenqing He, Benedetta Urbini, Roberta Gafà, Linda Ulazzi, Slav Yartsev, Glenn Bauman, Ting-Yim Lee, Enrico Fainardi

Medical Biophysics Publications

Patients with high-grade gliomas usually have heterogeneous response to surgery and chemoirradiation. The objectives of this study were (1) to evaluate serial changes in tumor volume and perfusion imaging parameters and (2) to determine the value of these data in predicting overall survival (OS). Twenty-nine patients with World Health Organization grades III and IV gliomas underwent magnetic resonance (MR) and computed tomography (CT) perfusion examinations before surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of tumor volumes and perfusion parameters were evaluated by receiver operating characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier survival analysis …

In-Vivo Longitudinal Mri Study: An Assessment Of Melanoma Brain Metastases In A Clinically Relevant Mouse Model., Mariama N Henry, Yuhua Chen, Catherine D Mcfadden, Felicia C Simedrea, Paula J Foster

Medical Biophysics Publications

Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a …

Impact Of Incremental Perfusion Loss On Oxygen Transport In A Capillary Network Mathematical Model., Graham M Fraser, Michael D Sharpe, Daniel Goldman, Christopher G Ellis

Medical Biophysics Publications

OBJECTIVES: To quantify how incremental capillary perfusion loss, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport.

METHODS: A computational model was applied to capillary networks with dimensions 84x168x342 (NI) and 70x157x268 (NII) μm, reconstructed in vivo from rat skeletal muscle. Functional capillary density (FCD) loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis.

RESULTS: A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under …

The Dissociative Subtype Of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity Of Basolateral And Centromedial Amygdala Complexes., Andrew A Nicholson, Maria Densmore, Paul A Frewen, Jean Théberge, Richard W J Neufeld, Margaret C Mckinnon, Ruth A Lanius

Medical Biophysics Publications

Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared to controls. Here, we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioural symptoms. PTSD patients (n=49), with (n=13) and without (n=36) the dissociative subtype, and age-matched healthy …

A Biomechanical Approach For In Vivo Lung Tumor Motion Prediction During External Beam Radiation Therapy, Abbas Samani, Elham Karami, Ting-Yim Lee, Stewart Gaede

Medical Biophysics Publications

No abstract provided.

Collectivization Of Vascular Smooth Muscle Cells Via Tgf-Β-Cadherin-11-Dependent Adhesive Switching., Brittany Balint, Hao Yin, Subrata Chakrabarti, Michael W A Chu, Stephen M Sims, J Geoffrey Pickering

Medical Biophysics Publications

OBJECTIVE: Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective.

APPROACH AND RESULTS: Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell-cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, ≤60 μm in length, which appeared …

Evidence Of Ventricular Contamination Of The Optical Signal In Preterm Neonates With Post Hemorrhagic Ventricle Dilation, J Kishimoto, M Diop, S De Ribaupierre, Dsc Lee, K St. Lawrence

Medical Biophysics Publications

No abstract provided.

Resting State And Diffusion Neuroimaging Predictors Of Clinical Improvements Following Constraint-Induced Movement Therapy In Children With Hemiplegic Cerebral Palsy., Kathryn Y Manning, Darcy Fehlings, Ronit Mesterman, Jan Willem Gorter, Lauren Switzer, Craig Campbell, Ravi S Menon

Medical Biophysics Publications

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with …

Investigation Of The Best Model To Characterize Diffuse Correlation Spectroscopy Measurements Acquired Directly On The Brain, K Verdecchia, M Diop, K St. Lawrence

Medical Biophysics Publications

No abstract provided.

Follow-Up Of Patients After Stereotactic Radiation For Lung Cancer: A Primer For The Nonradiation Oncologist., Kitty Huang, David A Palma

Medical Biophysics Publications

BACKGROUND: The use of stereotactic ablative radiotherapy (SABR) as primary treatment for early stage non-small-cell lung cancer, or for ablation of metastases, has increased rapidly in the past decade. With local recurrence rates reported at approximately 10%, and a patient population that is becoming increasingly fit and amenable to salvage treatment, appropriate multidisciplinary follow-up care is critical. Appropriate follow-up will allow for detection and management of radiation-related toxicity, early detection of recurrent disease and differentiation of recurrence from radiation-induced lung injury.

METHODS: This narrative review summarizes issues surrounding follow-up of patients treated with SABR in the context of a multidisciplinary …

Effect Of Taper Design On Trunnionosis In Metal On Polyethylene Total Hip Arthroplasty., Sok Chuen Tan, Matthew G Teeter, Christopher Del Balso, James L Howard, Brent A Lanting

Medical Biophysics Publications

This study examines how taper design affects corrosion and fretting at the head trunnion surface. All hip prostheses retrieved between 1999 and 2013 with 28mm/+0 heads were selected, resulting in 44 cobalt-chrome-on-polyethylene implants, representing six taper designs. Mean implantation time: 8.9±3.7years. The femoral head tapers were scored for fretting and corrosion using the Goldberg scale as both a combined score and by three zones (apex, central and base). There was no difference in age (P=0.34), BMI (P=0.29), or implantation time (P=0.19) between taper groups. The 11/13 taper had the highest combined corrosion and fretting score, but no difference (P=0.22) between …

Effect Of Ascorbate On Plasminogen Activator Inhibitor-1 Expression And Release From Platelets And Endothelial Cells In An In-Vitro Model Of Sepsis., Scott B Swarbreck, Dan Secor, Christopher G Ellis, Michael D Sharpe, John X Wilson, Karel Tyml

Medical Biophysics Publications

The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by …

Dynamic Perfusion Ct In Brain Tumors., Timothy Pok Chi Yeung, Glenn Bauman, Slav Yartsev, Enrico Fainardi, David Macdonald, Ting-Yim Lee

Medical Biophysics Publications

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented.

A Proposed Framework For Consensus-Based Lung Tumour Volume Auto-Segmentation In 4d Computed Tomography Imaging., Spencer Martin, Mark Brophy, David Palma, Alexander V Louie, Edward Yu, Brian Yaremko, Belal Ahmad, John L Barron, Steven S Beauchemin, George Rodrigues, Stewart Gaede

Medical Biophysics Publications

This work aims to propose and validate a framework for tumour volume auto-segmentation based on ground-truth estimates derived from multi-physician input contours to expedite 4D-CT based lung tumour volume delineation. 4D-CT datasets of ten non-small cell lung cancer (NSCLC) patients were manually segmented by 6 physicians. Multi-expert ground truth (GT) estimates were constructed using the STAPLE algorithm for the gross tumour volume (GTV) on all respiratory phases. Next, using a deformable model-based method, multi-expert GT on each individual phase of the 4D-CT dataset was propagated to all other phases providing auto-segmented GTVs and motion encompassing internal gross target volumes (IGTVs) …

Registration Of In-Vivo To Ex-Vivo Mri Of Surgically Resected Specimens: A Pipeline For Histology To In-Vivo Registration., Maged Goubran, Sandrine De Ribaupierre, Robert R Hammond, Catherine Currie, Jorge G Burneo, Andrew G Parrent, Terry M Peters, Ali R Khan

Medical Biophysics Publications

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology.

NEW METHOD: A combination of image-based and landmark-based 3D …

Right Ventricular Segmentation In Cardiac Mri With Moving Mesh Correspondences., Kumaradevan Punithakumar, Michelle Noga, Ismail Ben Ayed, Pierre Boulanger

Medical Biophysics Publications

This study investigates automatic propagation of the right ventricle (RV) endocardial and epicardial boundaries in 4D (3D+time) magnetic resonance imaging (MRI) sequences. Based on a moving mesh (or grid generation) framework, the proposed algorithm detects the endocardium and epicardium within each cardiac phase via point-to-point correspondences. The proposed method has the following advantages over prior RV segmentation works: (1) it removes the need for a time-consuming, manually built training set; (2) it does not make prior assumptions as to the intensity distributions or shape; (3) it provides a sequence of corresponding points over time, a comprehensive input that can be …

Feasibility Of A Unified Approach To Intensity-Modulated Radiation Therapy And Volume-Modulated Arc Therapy Optimization And Delivery, Jerry J. Battista, Michael Macfarlane, Eugene Wong, Jeff Z. Chen, Douglas A. Hoover

Medical Biophysics Publications

Purpose:

To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT)optimization and delivery to produce superior radiation treatment plans, both in terms of dosedistribution and efficiency of beam delivery when compared with either VMAT or IMRT alone.

Methods:

An inverse planning algorithm for UIMAT was prototyped within the pinnacle treatment planningsystem (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse …

Pulmonary Imaging Abnormalities In An Adult Case Of Congenital Lobar Emphysema., Damien Pike, Sindu Mohan, Weijing Ma, James F Lewis, Grace Parraga

Medical Biophysics Publications

Congenital lobar emphysema is mainly diagnosed in infants, although rare cases are reported in adults. A 20-yr-old female with acute dyspnea, chest pain and left upper lobe (LUL) chest x-ray hyperlucency underwent 3He magnetic resonance imaging (MRI) for ventilation and apparent diffusion coefficient (ADC) measurements, as well as CT for emphysema and airway wall measurements. Forced expiratory volume in 1s, residual volume, and airways-resistance were abnormal, but there was normal carbon-monoxide-diffusing-capacity. The LUL relative area of the density histogram

Pulmonary Abnormalities And Carotid Atherosclerosis In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Tamas J Lindenmaier, Khadija Sheikh, Casey E Neron, Daniel G Hackam, J David Spence, Aaron Fenster, Nigel A M Paterson, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Abstract It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 …

Rapid Desiccation Hardening Changes The Cuticular Hydrocarbon Profile Of Drosophila Melanogaster., Joseph R Stinziano, Richard J Sové, Howard D Rundle, Brent J Sinclair

Medical Biophysics Publications

The success of insects in terrestrial environments is due in large part to their ability to resist desiccation stress. Since the majority of water is lost across the cuticle, a relatively water-impermeable cuticle is a major component of insect desiccation resistance. Cuticular permeability is affected by the properties and mixing effects of component hydrocarbons, and changes in cuticular hydrocarbons can affect desiccation tolerance. A pre-exposure to a mild desiccation stress increases duration of desiccation survival in adult female Drosophila melanogaster, via a decrease in cuticular permeability. To test whether this acute response to desiccation stress is due to a change …

Skeletal Muscle Fibrosis In The Mdx/Utrn+/- Mouse Validates Its Suitability As A Murine Model Of Duchenne Muscular Dystrophy, Lisa M. Hoffman, William T. Hrinivich, Kelly M. Gutpell

Medical Biophysics Publications

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and …

Feasibility Of Simultaneous Whole-Brain Imaging On An Integrated Pet-Mri System Using An Enhanced 2-Point Dixon Attenuation Correction Method., Udunna C Anazodo, Jonathan D Thiessen, Tracy Ssali, Jonathan Mandel, Matthias Günther, John Butler, William Pavlosky, Frank S Prato, R Terry Thompson, Keith S St Lawrence

Medical Biophysics Publications

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.

METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose …

A Method For 3d Histopathology Reconstruction Supporting Mouse Microvasculature Analysis., Yiwen Xu, J Geoffrey Pickering, Zengxuan Nong, Eli Gibson, John-Michael Arpino, Hao Yin, Aaron D Ward

Medical Biophysics Publications

Structural abnormalities of the microvasculature can impair perfusion and function. Conventional histology provides good spatial resolution with which to evaluate the microvascular structure but affords no 3-dimensional information; this limitation could lead to misinterpretations of the complex microvessel network in health and disease. The objective of this study was to develop and evaluate an accurate, fully automated 3D histology reconstruction method to visualize the arterioles and venules within the mouse hind-limb. Sections of the tibialis anterior muscle from C57BL/J6 mice (both normal and subjected to femoral artery excision) were reconstructed using pairwise rigid and affine registrations of 5 µm-thick, paraffin-embedded …

Magnetic Resonance Imaging Biomarkers Of Chronic Obstructive Pulmonary Disease Prior To Radiation Therapy For Non-Small Cell Lung Cancer., Khadija Sheikh, Dante P I Capaldi, Douglas A Hoover, David A Palma, Brian P Yaremko, Grace Parraga

Medical Biophysics Publications

OBJECTIVE: In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients.

MATERIALS AND METHODS: Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram

RESULTS: Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = …

Pretreatment Of Human Cerebrovascular Endothelial Cells With Co-Releasing Molecule-3 Interferes With Jnk/Ap-1 Signaling And Suppresses Lps-Induced Proadhesive Phenotype., Fukashi Serizawa, Eric Patterson, Richard F Potter, Douglas D Fraser, Gediminas Cepinskas

Medical Biophysics Publications

OBJECTIVE: Exogenously administered CO interferes with PMN recruitment to the inflamed organs. The mechanisms of CO-dependent modulation of vascular proadhesive phenotype, a key step in PMN recruitment, are unclear.

METHODS: We assessed the effects/mechanisms of CO liberated from a water-soluble CORM-3 on modulation of the proadhesive phenotype in hCMEC/D3 in an in vitro model of endotoxemia. To this end, hCMEC/D3 were stimulated with LPS (1 μg/mL) for six hours. In some experiments hCMEC/D3 were pretreated with CORM-3 (200 μmol/L) before LPS-stimulation. PMN rolling/adhesion to hCMEC/D3 were assessed under conditions of laminar shear stress (0.7 dyn/cm(2) ). In parallel, expression of …

Unified Voxel- And Tensor-Based Morphometry (Uvtbm) Using Registration Confidence., Ali R Khan, Lei Wang, Mirza Faisal Beg

Medical Biophysics Publications

Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) both rely on spatial normalization to a template and yet have different requirements for the level of registration accuracy. VBM requires only global alignment of brain structures, with limited degrees of freedom in transformation, whereas TBM performs best when the registration is highly deformable and can achieve higher registration accuracy. In addition, the registration accuracy varies over the whole brain, with higher accuracy typically observed in subcortical areas and lower accuracy seen in cortical areas. Hence, even the determinant of Jacobian of registration maps is spatially varying in their accuracy, and combining these …