Swen Hesse’s research while affiliated with University Hospital Leipzig and other places

Background/Objectives: Positron emission tomography (PET) imaging with radiolabeled amino acids is increasingly used in glioma patients for biopsy planning, tumor delineation, prognostication, and therapy response assessment. This study investigated whether baseline amino acid PET imaging could identify regions at risk of future tumor recurrence. Methods: Retrospective case series of 14 patients with high-grade glioma. Contrast-enhanced magnetic resonance imaging (MRI) data of tumor recurrence and baseline imaging (PET-MRI) were co-registered. Volumes of interest (VOIs) of the high-grade glioma were derived from contrast-enhanced MRI at baseline and follow-up and from amino acid PET at baseline. The Dice similarity coefficient (DSC) was used to assess the overlap between VOIs. Furthermore, dynamic and static PET parameters were compared between the VOIs derived from contrast-enhanced MRI at follow-up and from the region of increased amino acid transport at baseline. Results: Regions of tumor recurrence in high-grade glioma patients overlap significantly more with baseline regions of increased amino acid transport on PET compared to regions of contrast enhancement on baseline MRI (p < 0.001). However, the static and dynamic PET statistics did not differentiate between regions that would later develop tumor recurrence and other areas of increased amino acid transport at baseline. Conclusions: These findings reaffirm the ability of amino acid PET to visualize the infiltrative components of gliomas not detected by contrast-enhanced MRI. Also, this study supports the role of amino acid PET in visualizing glioma infiltration beyond the MRI-visible tumor, but also indicates that accurately predicting the specific regions of recurrence based on baseline PET remains limited.

Background Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission. Methods This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[ ¹⁸ F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN. Results A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[ ¹⁸ F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN. Conclusions In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.

Purpose Heterogeneity in clinical phenotypes has led to the description of different phenotypes of Alzheimer’s disease (AD). Besides the most frequent amnestic variant of AD (aAD), patients presenting with language deficits are diagnosed with logopenic variant primary progressive aphasia (lvPPA), whereas patients presenting with visual deficits are classified as posterior cortical atrophy (PCA). Methods This study set out to investigate the value of a multi-parametric [¹⁸F]PI-2620 tau PET/MRI protocol to distinguish aAD, lvPPA and PCA to support clinical diagnosis in 32 patients. Phenotype-specific information about tau accumulation, relative perfusion, grey matter density, functional network alterations and white matter microstructural alterations was collected. Results The aAD patients showed significantly higher tau accumulation, relative hypoperfusion and grey matter density loss in the temporal lobes compared to PCA and lvPPA patients. PCA patients, on the other hand, showed significantly higher tau accumulation in the occipital lobe as compared to aAD patients. Relative hypoperfusion in the occipital lobe and loss of functional connectivity of the posterior cingulate cortex to supplementary visual cortical regions helped to distinguish PCA from lvPPA. Tau accumulation in the cerebellum and microstructural changes in the cingulum were found to help differentiate lvPPA from aAD. Conclusion This study highlights structural and functional differences between patients with different AD phenotypes. Differences in regional tau PET signals suggest that refinements in the Braak staging system are needed for the non-aAD cases. These patterns of tau accumulation align with the cascading network failure hypothesis, though more research is needed to warrant the here presented results in larger patient cohorts.

Obesity and the associated medical sequelae pose a major challenge for healthcare systems worldwide [...]

Successful motor skill acquisition requires the dynamic interaction of multiple brain regions, with the striatum playing a critical role in this network. Animal studies suggest that dopaminergic mechanisms are involved in the regulation of motor learning–associated striatal plasticity. In humans, however, the contribution of nigrostriatal dopaminergic transmission to motor learning remains elusive beyond its well-characterized role in initiation and fluent execution of movements. In this prospective observational study, we investigated motor sequence learning in individuals who had undergone 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography for the differential diagnosis of Parkinson's disease (n = 41) and age-matched healthy controls (n = 20). We found that striatal dopamine transporter depletion exhibited distinct spatial patterns that were associated with impairments in motor sequence learning and the manifestation of Parkinsonian motor symptoms, respectively. Specifically, significant associations between striatal dopamine transporter depletion and impairments in motor sequence learning were confined to posterior putaminal regions, whereas significant associations of striatal dopamine transporter depletion with Parkinsonian motor symptom severity showed a widespread spatial pattern across the entire striatal volume with an anterior maximum. Normative functional connectivity analysis revealed that both behavioural domains shared largely overlapping connectivity patterns with the basal ganglia and supplementary motor area. However, apart from connectivity with more posterior parts of the supplementary motor area, significant functional connectivity with primary motor cortical areas was only present for striatal dopamine transporter availability–related modulation of online motor learning. Our findings indicate that striatal dopaminergic signalling plays a specific role in motor sequence learning beyond its influence on mere motor execution, implicating learning-related sensorimotor striatum recruitment and cortico-striatal plasticity as dopamine-dependent mechanisms.

Kurze Einleitung zum Fall: Eine 46-jährige nierauchende Büroangestellte stellte sich mit starken linksthorakalen Schmerzen (8/10), bestehend seit 6 Wochen, vor. Sie beklagte einen ungewollten Gewichtsverlust von 3 kg und zunehmende Belastungsluftnot. In der Vorgeschichte waren keine akuten Infektionen, Traumata, chronischen Erkrankungen oder Tumorleiden bekannt. Klinisch fielen basal linksseitig ein abgeschwächtes Atemgeräusch, ein fehlender Stimmfremitus sowie ein hyposonorer Klopfschall auf. Laborchemisch war alleinig die Laktat-Dehydrogenase gering erhöht. Ein Röntgen-Thorax, eine Thorax-Computertomografie (CT), eine Thorax-Sonografie und eine 18F-Fluordesoxyglukose (FDG)-Positronenemissionstomografie (PET) zeigten die folgenden Befunde ([Abb. 1], [Abb. 2]). FRAGEN Welche pathologischen Befunde sind sichtbar? Erlauben diese Befunde eine Diagnose? Wenn ja, welche? Sind Differenzialdiagnosen möglich? Wenn ja, welche? Welche weitere Diagnostik ist notwendig?

Background Cancer‐associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non‐imaging criteria. Given the metabolic underpinnings of CAC and the ability of [¹⁸F]fluoro‐2‐deoxy‐D‐glucose (FDG)‐positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole‐body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. Methods This multi‐centre study included 345 LCP who underwent WB [¹⁸F]FDG‐PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into ‘No CAC’ (WLGS‐0/1 at baseline prior treatment and at first follow‐up: N = 158, 51F/107M), ‘Dev CAC’ (WLGS‐0/1 at baseline and WLGS‐3/4 at follow‐up: N = 90, 34F/56M), and ‘CAC’ (WLGS‐3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake ( ) and CT‐defined volumes were extracted for abdominal and visceral organs, muscles, and adipose‐tissue using automated image segmentation of baseline [¹⁸F]FDG‐PET/CT images. Imaging and non‐imaging parameters from laboratory tests were compared statistically. A machine‐learning (ML) model was then trained to classify LCP as ‘No CAC’, ‘Dev CAC’, and ‘CAC’ based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. Results The three CAC categories displayed multi‐organ differences in . In all target organs, was higher in the ‘CAC’ cohort compared with ‘No CAC’ (P < 0.01), except for liver and kidneys, where in ‘CAC’ was reduced by 5%. The ‘Dev CAC’ cohort displayed a small but significant increase in of pancreas (+4%), skeletal‐muscle (+7%), subcutaneous adipose‐tissue (+11%), and visceral adipose‐tissue (+15%). In ‘CAC’ patients, a strong negative Spearman correlation (ρ = −0.8) was identified between and volumes of adipose‐tissue. The machine‐learning model identified ‘CAC’ at baseline with 81% of accuracy, highlighting of spleen, pancreas, liver, and adipose‐tissue as most relevant features. The model performance was suboptimal (54%) when classifying ‘Dev CAC’ versus ‘No CAC’. Conclusions WB [¹⁸F]FDG‐PET/CT imaging reveals groupwise differences in the multi‐organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi‐centre study has been initiated to address the limitations of the present retrospective analysis.