Michael Brehler

• Dr. sc. hum.
• Scientific Project Manager at University Medical Center Hamburg - Eppendorf

Background: Prostate cancer (PCa) is among the most common cancers in men and its diagnosis requires the histopathological evaluation of biopsies by human experts. While several recent artificial intelligence-based (AI) approaches have reached human expert-level PCa grading, they often display significantly reduced performance on external datasets....

Background Membranous nephropathy (MN) is caused by autoantibody binding to podocyte foot process antigens such as THSD7A and PLA 2 R1. The mechanisms of the glomerular antigen/autoantibody deposition and clearance are unknown. Methods We explore the origin and significance of glomerular accumulations in (1) diagnostic and follow-up biospecimens f...

Background Membranous nephropathy (MN) is caused by autoantibody binding to podocyte foot process antigens such as THSD7A and PLA2R1. The mechanisms of the glomerular antigen/autoantibody deposition and clearance are unknown. Methods We explore the origin and significance of glomerular accumulations in (1) diagnostic and follow-up biospecimens from...

BACKGROUND AND OBJECTIVES This study identified a clinically significant subset of patients with glioma with tumor outside of contrast enhancement present at autopsy and subsequently developed a method for detecting nonenhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps wou...

Prostate cancer is among the most common cancers in men with around 1.4 million new cases each year world-wide. A vital part in the diagnosis of prostate cancer is the evaluation of its severity using biopsies and histopathology. Recent progress in artificial intelligence-based image analysis has led to a flurry of algorithms for the automated anal...

Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative...

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems¹. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to ligh...

One in eight men will be affected by prostate cancer (PCa) in their lives. While the current clinical standard prognostic marker for PCa is the Gleason score, it is subject to inter-reviewer variability. This study compares two machine learning methods for discriminating between cancerous regions on digitized histology from 47 PCa patients. Whole-s...

PURPOSE Glioblastoma is one of the most common and deadly adult brain tumors. Current standard treatment is surgical resection followed by radiation and concomitant chemotherapy (chemoRT). Glioblastoma progression is monitored using MRI, primarily relying on post-contrast T1-weighted imaging (T1C). Unfortunately, tumor invasion is known to extend b...

Background: One in eight men will be affected by prostate cancer (PCa) in their lives. While the current clinical standard prognostic marker for PCa is the Gleason score, it is subject to inter-reviewer variability. This study compares two machine learning methods for discriminating between high- and low-grade PCa on histology from 47 PCa patients....

The latent space of a generative adversarial network (GAN) may model pathologically-significant semantics with unsupervised learning. To explore this phenomenon, we trained and tested a StyleGAN2 on a high quality prostate histology dataset covering the prostate cancer (PCa) diagnostic spectrum. Our pathologist annotated synthetic images to identif...

Background This study identified a clinically significant subset of glioma patients with tumor outside of contrast-enhancement present at autopsy, and subsequently developed a method for detecting non-enhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps would be able to non-...

Background and purpose: Currently, contrast-enhancing margins on T1WI are used to guide treatment of gliomas, yet tumor invasion beyond the contrast-enhancing region is a known confounding factor. Therefore, this study used postmortem tissue samples aligned with clinically acquired MRIs to quantify the relationship between intensity values and cel...

The presence and extent of cribriform patterned Gleason 4 (G4) glands are associated with poor prognosis following radical prostatectomy. This study used whole-mount prostate histology and multiparametric magnetic resonance imaging (MP-MRI) to evaluate diffusion differences in G4 gland morphology. Fourty-eight patients underwent MP-MRI prior to pro...

Tumor heterogeneity in glioblastoma complicates delineation of active tumor using standard MR imaging. Pseudo-progression following treatment with chemotherapy and radiation (chemoRT) further complicates how tumors appear. T1-weighted subtraction maps (T1S) have been used to better identify subtly enhancing regions containing infiltrative tumor. Th...

Tumor treating fields (TTFields) are thought to disrupt the cell division process in glioma. This study uses autopsy tissue samples from patients recruited for brain donation to determine whether TTFields treatment duration and usage affects cellularity distributions beyond the gadolinium contrast enhancing region on T1-weighted (T1w) magnetic reso...

Infiltrative glioma beyond contrast enhancement on MRI is often difficult to identify with conventional imaging. In this study, we use large-format autopsy samples aligned to multi-parametric MRI to test the hypothesis that radio-pathomic machine learning models are able to accurately identify areas of infiltrative tumor beyond the contrast enhanci...

Background Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. Purpose To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer...

e14035 Background: With an average overall survival of 12-18 months, glioblastoma has a particularly grim diagnosis. Standard treatment of glioblastoma, following detection on MRI, is surgical resection followed by radiation therapy and chemotherapy and is monitored through MR imaging. Glioblastoma has a unique heterogenous nature that complicates...

Current MRI signatures of brain cancer often fail to identify regions of hypercellularity beyond the contrast enhancing region. Therefore, this study used autopsy tissue samples aligned to clinical MRIs in order to quantify the relationship between intensity values and cellularity, as well as to develop a radio-pathomic model to predict cellularity...

Background Over one-half of all cancer patients receive radiation therapy (RT). However, radiation exposure to the heart can cause cardiotoxicity. Nevertheless, there is a paucity of data on RT-induced cardiac damage, with limited understanding of safe regional RT doses, early detection, prevention, and management. A common initial feature of cardi...

PURPOSE Tumor treatment fields (TTFields) are approved by the FDA for newly diagnosed as well as recurrent glioblastoma (GBM). TTFields have been shown to extend survival by 4.9 months in newly diagnosed GBM, and a landmark overall survival rate of 13% at 5 years. However, the specific effects remain widely unknown, which has prevented widespread c...

This study used autopsy tissue samples taken from patients with glioblastoma who had undergone Tumor-Treating Fields (TTFields) therapy to examine the effects of treatment usage and duration on cellular and mitotic activity distributions. We hypothesized that treatment duration and percent compliance would be associated with a change in cellularity...

This study used large format autopsy tissue samples to compare radio-pathomic maps of brain cancer to a current tumor segmentation algorithm. We hypothesized that an MRI-based machine learning model trained with actual histology rather than radiologist annotations cellularity would 1) improve delineation between tumor and treatment effect, and 2) d...

Purpose: Our study predictively maps epithelium density in magnetic resonance imaging (MRI) space while varying the ground truth labels provided by five pathologists to quantify the downstream effects of interobserver variability. Approach: Clinical imaging and postsurgical tissue from 48 recruited prospective patients were used in our study. Tissu...

Magnetic resonance (MR)-derived radiomic features have shown substantial predictive utility in modeling different prognostic factors of glioblastoma and other brain cancers. However, the biological relationship underpinning these predictive models has been largely unstudied, and the generalizability of these models had been called into question. He...

Background Anterior cruciate ligament (ACL) injury is a military occupational hazard that may be attributed to an individual’s knee biomechanics and joint anatomy. This study sought to determine if greater flexion when landing with load resulted in knee biomechanics thought to decrease ACL injury risk and whether knee biomechanics during landing re...

MR-derived radiomic features have demonstrated substantial predictive utility in modeling different prognostic factors of glioblastomas and other brain cancers. However, the biological relationship underpinning these predictive models has been largely unstudied, with the generalizability of these models also called into question. Here, we examine t...

We present an algorithm for automatic anatomical measurements in tomographic datasets of the knee. The algorithm uses a set of atlases, each consisting of a knee image, surface segmentations of the bones, and locations of landmarks required by the anatomical metrics. A multistage volume-to-volume and surface-to-volume registration is performed to t...

Purpose: We develop an Active Shape Model (ASM) framework for automated bone segmentation and anatomical landmark localization in weight-bearing Cone-Beam CT (CBCT). To achieve a robust shape model fit in narrow joint spaces of the foot (0.5 - 1 mm), a new approach for incorporating proximity constraints in ASM (coupled ASM, cASM) is proposed. Me...

Purpose: A high-resolution cone-beam CT (CBCT) system for extremity imaging has been developed using a custom complementary metal-oxide-semiconductor (CMOS) x-ray detector. The system has spatial resolution capability beyond that of recently introduced clinical orthopedic CBCT. We evaluate performance of this new scanner in quantifying trabecular...

Objective To evaluate the influence of weight-bearing (WB) load in standard axial ankle syndesmotic measurements using cone beam CT (CBCT) examination of asymptomatic uninjured ankles. Materials and methods In this IRB approved, prospective study, patients with previous unilateral ankle fractures were recruited. We simultaneously scanned the injur...

PURPOSE To improve robustness of Active Shape Model (ASM) segmentation of bones separated by narrow joint spaces, we develop a coupled ASM (cASM) that simultaneously segments neighboring bones using their individual statistical shape models (SSM) and a proximity constraint. MATERIAL AND METHODS The study involved segmentation of Talus and Calcaneus...

In-vivo evaluation of bone microarchitecture remains challenging because of limited resolution of conventional orthopaedic imaging modalities. We investigate the performance of flat-panel detector extremity Cone-Beam CT (CBCT) in quantitative analysis of trabecular bone. To enable accurate morphometry of fine trabecular bone architecture, advanced...

Purpose: A prototype high-resolution extremity cone-beam CT (CBCT) system based on a CMOS detector was developed to support quantitative in vivo assessment of bone microarchitecture. We compare the performance of CMOS CBCT to an amorphous silicon (a-Si:H) FPD extremity CBCT in imaging of trabecular bone. Methods: The prototype CMOS-based CBCT in...

We present a novel reconstruction algorithm based on a general cone-beam CT forward model which is capable of incorporating the blur and noise correlations that are exhibited in flat-panel CBCT measurement data. Specifically, the proposed model may include scintillator blur, focal-spot blur, and noise correlations due to light spread in the scintil...

We present a novel reconstruction algorithm based on a general cone-beam CT forward model which is capable of incorporating the blur and noise correlations that are exhibited in flat-panel CBCT measurement data. Specifically, the proposed model may include scintillator blur, focal-spot blur, and noise correlations due to light spread in the scintil...

PURPOSE An automated algorithm was developed for measurements of bone morphology and joint alignment in volumetric musculoskeletal imaging. The algorithm was applied to evaluation of the weight-bearing tibiofemoral and patellofemoral joints using a dedicated extremity cone-beam CT (CBCT) system. METHOD AND MATERIALS Weight-bearing CBCT scans were...

Purpose: Quantitative assessment of trabecular bone microarchitecture in extremity cone-beam CT (CBCT) would benefit from the high spatial resolution, low electronic noise, and fast scan time provided by complementary metal-oxide semiconductor (CMOS) x-ray detectors. We investigate the performance of CMOS sensors in extremity CBCT, in particular w...

Purpose: Anatomical metrics of the tibiofemoral joint support assessment of joint stability and surgical planning. We propose an automated, atlas-based algorithm to streamline the measurements in 3D images of the joint and reduce user-dependence of the metrics arising from manual identification of the anatomical landmarks. Methods: The method is...

Purpose: CMOS x-ray detectors offer small pixel sizes and low electronic noise that may support the development of novel high-resolution imaging applications of cone-beam CT (CBCT). We investigate the effects of CsI scintillator thickness on the performance of CMOS detectors in high resolution imaging tasks, in particular in quantitative imaging o...

PURPOSE Bone microstructure is a potential biomarker in osteoporosis and osteoarthritis. Extremities cone-beam CT (CBCT) is a compelling platform for in-vivo bone morphometrics owing to the high resolution of flat-panel detectors (FPDs) that supports assessment of trabeculae. Improvement in spatial resolution of extremities CBCT is anticipated with...

Purpose:Extremity cone-beam CT (CBCT) with an amorphous silicon (aSi) flat-panel detector (FPD) provides low-dose volumetric imaging with high spatial resolution. We investigate the performance of the newer complementary metal-oxide semiconductor (CMOS) detectors to enhance resolution of extremities CBCT to ∼0.1 mm, enabling morphological analysis...

Purpose: In orthopedic surgeries, it is important to avoid intra-articular implant placements, which increase revision rates and the risk of arthritis. In order to support the intraoperative assessment and correction of surgical implants, we present an automatic detection approach using cone-beam computed tomography (CBCT). Methods: Multiple act...

Purpose: The assessment of intra-operatively acquired volumetric data is a difficult and often time-consuming task, which demands a new set of skills from the surgeons. In the case of orthopedic surgeries such as the treatment of calcaneal fractures, the correctness of the reduction of the bone fragments can be verified with the help of C-arm CT v...

With the help of an intra-operative mobile C-arm CT, medical interventions can be verified and corrected, avoiding the need for a post-operative CT and a second intervention. An exact adjustment of standard plane positions is necessary for the best possible assessment of the anatomical regions of interest but the mobility of the C-arm causes the ne...

The use of intra-operative 3D imaging is more and more becoming a standard process in orthopedic surgery. By providing better spatial visualization with nearly the image quality of a conventional CT scanner the C-arm CT can help the surgeon to verify the results of the surgery and thus reduces the need for second interventions. In literature, the i...

Orthopedic fractures are often fixed using metal implants. The correct positioning of cylindrical implants such as surgical screws, rods and guide wires is highly important. Intraoperative 3D imaging is often used to ensure proper implant placement. However, 3D image interaction is time-consuming and requires experience. We developed an automatic m...

Intraarticular fractures of the calcaneus are routinely treated by open reduction and internal fixation followed by intraoperative imaging to validate the repositioning of bone fragments. C-Arm CT offers surgeons the possibility to directly verify the alignment of the fracture parts in 3D. Although the device provides more mobility, there is no suf...

Calcaneal fractures are commonly treated by open reduction and internal fixation. An anatomical reconstruction of involved joints is mandatory to prevent cartilage damage and premature arthritis. In order to avoid intraarticular screw placements, the use of mobile C-arm CT devices is required. However, for analyzing the screw placement in detail, a...

Das Standardvorgehen bei der Behandlung von Calcaneusfrakturen ist eine Osteosynthese. Mit Hilfe der intraoperativen Bildgebung wie dem mobilen C-Bogen CT kann der Chirurg das Repositionsergebnis noch im Operationssaal verifizieren und wenn nötig korrigieren. Die Mobilität des C-Bogen CT hat jedoch zur Folge, dass Informationen über die Orientierun...

Frakturen am Fersenbein werden mit Hilfe offener Reduktion und interner Fixation korrigiert. Eine anatomisch korrekte Rekonstruktion beteiligter Gelenke ist notwendig, um Knorpelschäden und verfrühte Arthrose vorzubeugen. Um intraartikuläre Schraubenplatzierungen zu vermeiden wird der mobile 3D C-Bogen eingesetzt. Die detaillierte Analyse der Schra...

In a series of projects the genotype information of individuals is now combined with molecular phenotypes. When applied with transcriptomics or proteomics data, this allows to determine those chromosomal regions that are associated with the variation of a gene expression level. Such expression QTL, especially those located within QTL for clinical p...