Maximilian Ackermann

• Universitätsmedizin der Johannes Gutenberg-Universität Mainz

A bstract Biomedical systems span multiple spatial scales, encompassing tiny functional units to entire organs. Interpreting these systems through image segmentation requires the effective propagation and integration of information across different scales. However, most existing segmentation methods are optimised for single-scale imaging modalities...

Interstitial lung disease (ILD) is a clinical term that refers to a diverse group of non-neoplastic lung diseases. This group includes idiopathic and secondary pulmonary entities that are often associated with progressive pulmonary fibrosis. Currently, therapeutic approaches based on specific structural targeting of pulmonary fibrosis are limited t...

The human placenta exhibits a complex three dimensional (3D) structure with a complex interpenetrating vascular tree and large internal interfacial area. In a unique and yet insufficiently explored way, this parenchymal structure enables its multiple functions as a respiratory, renal, and gastrointestinal multiorgan. The histopathological states ar...

The vascular niche plays a crucial role in regulating hematopoiesis, and the presence of JAK2V617F endothelial cells (EC) in myeloproliferative neoplasms (MPN) underscores its therapeutic significance. Leveraging patient-specific induced pluripotent stem cells (iPSC) harboring JAK2WT or the MPN-driver JAK2V617F (heterozygous, JAK2V617F HET or homoz...

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonst...

Automated blood vessel segmentation is critical for biomedical image analysis, as vessel morphology changes are associated with numerous pathologies. Still, precise segmentation is difficult due to the complexity of vascular structures, anatomical variations across patients, the scarcity of annotated public datasets, and the quality of images. Our...

Automated blood vessel segmentation is critical for biomedical image analysis, as vessel morphology changes are associated with numerous pathologies. Still, precise segmentation is difficult due to the complexity of vascular structures, anatomical variations across patients, the scarcity of annotated public datasets, and the quality of images. Our...

Background Current clinical imaging modalities such as CT and MRI provide resolution adequate to diagnose cardiovascular diseases but cannot depict detailed structural features in the heart across length scales. Hierarchical phase-contrast tomography (HiP-CT) uses fourth-generation synchrotron sources with improved x-ray brilliance and high energie...

Background Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and...

In European countries, nearly 10% of all hospital admissions are related to respiratory diseases, mainly chronic life-threatening diseases such as COPD, pulmonary hypertension, IPF or lung cancer. The contribution of blood vessels and angiogenesis to lung regeneration, remodeling and disease progression has been increasingly appreciated. The vascul...

Background Changes in epithelial cell shape reflects optimal cell packing and the minimization of surface free energy, but also cell–cell interactions, cell proliferation, and cytoskeletal rearrangements. Results Here, we studied the structure of the rat pleura in the first 15 days after birth. After pleural isolation and image segmentation, the a...

Targeted drug delivery to visceral organs offers the possibility of not only limiting the required dose, but also minimizing drug toxicity; however, there is no reliable method for delivering drugs to the surface of visceral organs. Here, we used six color tracers and the chick chorioallantoic membrane (CAM) model to investigate the use of the hete...

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP...

In the later stages of angiogenesis, the vascular sprout transitions into a functional vessel by fusing with a target vessel. Although this process appears to routinely occur in embryonic tissue, the biologic rules for sprout fusion and lumenization in adult regenerating tissue are unknown. To investigate this process, we grafted portions of the re...

As the central organ of the respiratory system, the human lung is responsible for supplying oxygen to the blood, which reaches the erythrocytes by diffusion through the alveolar walls and is then distributed throughout the body. By exploiting the difference in electron density detected by a phase shift in soft tissue, high-resolution X-ray phase-co...

Mammalian epithelia form a continuous sheet of cells that line the surface of visceral organs. To analyze the epithelial organization of the heart, lung, liver and bowel, epithelial cells were labeled in situ , isolated as a single layer and imaged as large epithelial digitally combine montages. The stitched epithelial images were analyzed for geom...

Purpose: The corneal epithelium has a glycocalyx composed of membrane-associated glycoproteins, mucins, and galactin-3. Similar to the glycocalyx in visceral tissues, the corneal glycocalyx functions to limit fluid loss and minimize frictional forces. Recently, the plant-derived heteropolysaccharide pectin has been shown to physically entangle wit...

Purpose The aim of this study was to identify the monogenic cause of pulmonary arterial hypertension (PAH), a multifactorial and often fatal disease, in 2 unrelated consanguine families. Methods We performed exome sequencing and validated variant pathogenicity by whole-blood RNA and protein expression analysis in both families. Further RNA sequenc...

Background: The kidney vasculature is exquisitely structured to orchestrate renal function. Structural profiling of the vasculature in intact rodent kidneys, has provided insights into renal haemodynamics and oxygenation, but has never been extended to the human kidney beyond a few vascular generations. We hypothesised that synchrotron-based imagin...

Pectin is a heteropolysaccharide responsible for the structural integrity of the cell walls of terrestrial plants. When applied to the surface of mammalian visceral organs, pectin films form a strong physical bond with the surface glycocalyx. A potential mechanism of pectin adhesion to the glycocalyx is the water-dependent entanglement of pectin po...

Imaging across different scales is essential for understanding healthy organ morphology and pathophysiological changes. The macro- and microscale three-dimensional morphology of large samples, including intact human organs, is possible with X-ray microtomography (using laboratory or synchrotron sources). Preparation of large samples for high-resolu...

Treatment with oncolytic measles vaccines (MV) elicits activation of immune cells, including natural killer (NK) cells. However, we found that MV-activated NK cells show only modest direct cytotoxic activity against tumor cells. To specifically direct NK cells towards tumor cells, we developed oncolytic measles vaccines encoding bispecific killer e...

Hydrogels provide a promising method for the targeted delivery of protein drugs. Loading the protein drug into the hydrogel free volume can be challenging due to limited quantities of the drug (e.g., growth factor) and complex physicochemical properties of the hydrogel. Here, we investigated both passive and active loading of the heteropolysacchari...

Pleural epithelial adaptations to mechanical stress are relevant to both normal lung function and parenchymal lung diseases. Assessing regional differences in mechanical stress, however, has been complicated by the nonlinear stress–strain properties of the lung and the large displacements with ventilation. Moreover, there is no reliable method of i...

A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed...

Background COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9–20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of se...

Pectin is a plant-derived heteropolysaccharide that has been implicated in drug development, tissue engineering, and visceral organ repair. Pectin demonstrates remarkable biostability in a variety of physiologic environments but is biodegradable in water. To understand the dynamics of pectin biodegradation in basic environments, we developed a micr...

Objet L’architecture capillaire et la circulation bronchique habituelle semble sensiblement modifiée dans le cadre des pneumopathies à SARS-CoV-2, associés à des thromboses multiples [1], [2]. L’imagerie en contraste de phase par source synchrotron (sPCI) permet d’étudier précisément l’ensemble des tissus organiques à une résolution microscopique e...

Imaging the different scales of biological tissue is essential for understanding healthy organ behavior and pathophysiological changes. X-ray micro-tomography using both laboratory (μCT) and synchrotron sources (sCT) is a promising tool to image the 3D morphology at the macro- and micro-scale of large samples, including intact human organs. Prepara...

Background: The COVID-19 pandemic is the third worldwide coronavirus-associated disease outbreak in the past 20 years. Lung involvement, with acute respiratory distress syndrome (ARDS) in severe cases, is the main clinical feature of this disease; the cardiovascular system, the central nervous system, and the gastrointestinal tract can also be aff...

Hintergrund: Die COVID-19-Pandemie stellt den dritten weltweiten Coronavirus-assoziierten Erkrankungsausbruch der letzten 20 Jahre dar. Klinisch dominiert die pulmonale Beteiligung mit einem akuten Lungenversagen (ARDS) bei schweren Verläufen, jedoch können auch andere Organsysteme wie das Herz-Kreislauf-System, Zentralnervensystem und der Gastroin...

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows the decoupling of sample size and resolution while maintaining high sensitivity to the microstructures of soft, partially dehydrated tissues. The continuous developments in multiscale X-ray imaging resulted in hierarchical phase-contrast tomography,...

COVID-19 has been associated with a range of illness severity-from minimal symptoms to life-threatening multisystem organ failure. The severe forms of COVID-19 appear to be associated with an angiocentric or vascular phase of the disease. In studying autopsy patients succumbing to COVID-19, we found alveolar capillary microthrombi were 9 times more...

The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report tha...

Plant‐derived structural polymer, pectin, is the “glue” between plant cells, a biomaterial with promising performance as a sealant on visceral organs. However, the nature of bioabsorption and biodurability of pectin remains unclear. Here, we investigate the feasibility of a quantitative microfluidic perfusion assay based on photochemical quenching,...

The cornea presents unique challenges to wound care. The cornea is constantly exposed to bacterial colonization, has ongoing risk of wound‐related astigmatism, and is cumbersome for traditional wound dressings. A potential solution to these challenges is provided by the corneal glycocalyx. Recent high pressure rapid freezing fixation techniques sug...

Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. In this study, we analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n=7), one pulmonary arterial hypertension group (PAH, n=20), and one hea...

Children's interstitial lung disease (chILD) encompasses a wide and heterogeneous spectrum of diseases substantially different from that of adults. Established classification systems divide chILD into conditions more prevalent in infancy and other conditions occurring at any age. This categorisation is based on a multidisciplinary approach includin...

Pectin’s unique physicochemical properties have been linked to a variety of reparative and regenerative processes in nature. To investigate the effect of water on pectin repair, we used a 5 mm stainless-steel uniaxial load to fracture glass phase pectin films. The fractured gel phase films were placed on a 1.5–1.8 mm thick layer of water and incuba...

Pathology and radiology are complimentary tools, and their joint application is often crucial in obtaining an accurate diagnosis in non-neoplastic pulmonary diseases. However, both come with significant limitations of their own: Computed Tomography (CT) can only visualize larger structures due to its inherent–relatively–poor resolution, while (hist...

(1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within ≤7 and >7 da...

Muco-obstructive lung diseases are characterized by airway obstruction and hyperinflation, which can be quantified by imaging. Our aim was to evaluate µCT for longitudinal quantification of muco-obstructive lung disease in β-epithelial Na ⁺ channel overexpressing (Scnn1b-TG) mice and of the effects of neutrophil elastase (NE) knockout on its progre...

Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lun...

We have used phase-contrast X-ray tomography to characterize the three-dimensional (3d) structure of cardiac tissue from patients who succumbed to Covid-19. By extending conventional histopathological examination by a third dimension, the delicate pathological changes of the vascular system of severe Covid-19 progressions can be analyzed, fully qua...

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows to decouple sample size and resolution, while maintaining high sensitivity to the microstructure of soft, partially dehydrated tissues. The recently developed imaging technique, hierarchical phase-contrast tomography, is a comprehensive approach to...

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). The spatial cohe...

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 A...

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: We aimed to identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 sampl...

Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging...

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e...

Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monit...

For the first time, we have used phase-contrast x-ray tomography to characterize the three-dimensional (3d) structure of cardiac tissue from patients who succumbed to Covid-19. By extending conventional histopatholocigal examination by a third dimension, the delicate pathological changes of the vascular system of severe Covid-19 progressions can be...

Pleural injuries and the associated “air leak” are the most common complications after pulmonary surgery. Air leaks are the primary reason for prolonged chest tube use and increased hospital length of stay. Pectin, a plant-derived heteropolysaccharide, has been shown to be an air-tight sealant of pulmonary air leaks. Here, we investigate the morpho...

Anastomotic leakage is a frequent complication of intestinal surgery and a major source of surgical morbidity. The timing of anastomotic failures suggests that leaks are the result of inadequate mechanical support during the vulnerable phase of wound healing. To identify a biomaterial with physical and mechanical properties appropriate for assisted...

Overshooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombo...

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be...

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations ha...

Viral respiratory diseases constitute the most common reasons for hospitalization with more than half of all acute illnesses worldwide. Progressive respiratory failure with pronounced diffuse alveolar damage has been identified as the primary cause of death in COVID-19. COVID-19 pneumonia shares common histopathological hallmarks with influenza (H1...

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (Hi...

Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Although the overall survival following transplantation has generally improved over recent decades, long-time survival of lung and st...

Amorphous Ca-phosphate (ACP) particles stabilized by inorganic polyphosphate (polyP) were prepared by co-precipitation of calcium and phosphate in the presence of polyP (15% [w/w]). These hybrid nanoparticles showed no signs of crystallinity according to X-ray diffraction analysis, in contrast to the particles obtained at a lower (5% [w/w]) polyP c...

A drug encapsulation/delivery system using a novel principle is described that is based on an intra-particle migration of calcium ions between a central Ca²⁺-enriched nanoparticle core and the surrounding shell compartment. The supply of Ca²⁺ is needed for the formation of a coacervate shell around the nanoparticles, acting as the core of drug-load...

Cirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascula...

The mesothelium is a dynamic and specialized tissue layer that covers the somatic cavities (pleural, peritoneal, and pericardial) as well as the surface of the visceral organs such as the lung, heart, liver, bowel and tunica vaginalis testis. The potential therapeutic manipulation of visceral organs has been complicated by the carbohydrate surface...

Cement is used both as a construction material and for medical applications. Previously, it has been shown that the physiological polymer inorganic polyphosphate (polyP) is morphogenetically active in regeneration of skin, bone, and cartilage. The present study investigates the question if this polymer is also a suitable additive to improve the sel...

The distinguished property of the physiological polymer, of inorganic polyphosphate (polyP), is to act as a bio-intelligent material which releases stimulus-dependently metabolic energy to accelerate wound healing. This characteristic is based on the bio-imitating feature of polyP to be converted, upon exposure to peptide-containing body fluids, fr...