Ultrahigh resolution whole body photon counting computed tomography as a novel versatile tool for translational research from mouse to man.

X-ray computed tomography (CT) is a cardinal tool in clinical practice. It provides cross-sectional images within seconds. The recent introduction of clinical photon-counting CT allowed for an increase in spatial resolution by more than a factor of two resulting in a pixel size in the center of rotation of about 150 µm. This level of spatial resolution is in the order of dedicated preclinical micro-CT systems. However so far, the need for different dedicated clinical and preclinical systems often hinders the rapid translation of early research results to applications in men. This drawback might be overcome by ultra-high resolution (UHR) clinical photon-counting CT unifying preclinical and clinical research capabilities in a single machine. Herein, the prototype of a clinical UHR PCD CT (SOMATOM CounT, Siemens Healthineers, Forchheim, Germany) was used. The system comprises a conventional energy-integrating detector (EID) and a novel photon-counting detector (PCD). While the EID provides a pixel size of 0.6 mm in the centre of rotation, the PCD provides a pixel size of 0.25 mm. Additionally, it provides a quantification of photon energies by sorting them into up to four distinct energy bins. This acquisition of multi-energy data allows for a multitude of applications, e.g. pseudo-monochromatic imaging. In particular, we examine the relation between spatial resolution, image noise and administered radiation dose for a multitude of use-cases. These cases include ultra-high resolution and multi-energy acquisitions of mice administered with a prototype bismuth-based contrast agent (nanoPET Pharma, Berlin, Germany) as well as larger animals and actual patients. The clinical EID provides a spatial resolution of about 9 lp/cm (modulation transfer function at 10%, MTF10%) while UHR allows for the acquisition of images with up to 16 lp/cm allowing for the visualization of all relevant anatomical structures in preclinical and clinical specimen. The spectral capabilities of the system enable a variety of applications previously not available in preclinical research such as pseudo-monochromatic images. Clinical ultra-high resolution photon-counting CT has the potential to unify preclinical and clinical research on a single system enabling versatile imaging of specimens and individuals ranging from mice to man.

Dental imaging using an ultra-high resolution photon-counting CT system.

Clinical photon-counting CT (PCCT) offers a spatial resolution of about 200 µm and might allow for acquisitions close to conventional dental CBCTs. In this study, the capabilities of this new system in comparison to dental CBCTs shall be evaluated. All 8 apical osteolysis identified in CBCT were identified by both readers in all three PCCT scan protocols. Mean visibility scores showed statistical significant differences for root canals(p = 0.0001), periodontal space(p = 0.0090), cortical(p = 0.0003) and spongious bone(p = 0.0293) in favor of high and medium dose PCCT acquisitions. Overall, both devices showed excellent image quality of all structures assessed. Interrater-agreement showed high values for all protocols in all structures. Bland-Altman plots revealed a high concordance of both modalities with the reference measurements. In vitro, ultra-high resolution PCCT can reliably identify different diagnostic entities and structures relevant for dental diagnostics similar to conventional dental CBCT with similar radiation dose. Acquisitions of five cadaveric heads were performed in an experimental CT-system containing an ultra-high resolution PC detector (0.25 mm pixel size in isocenter) as well as in a dental CBCT scanner. Acquisitions were performed using dose levels of 8.5 mGy, 38.0 mGy and 66.5 mGy (CTDI16cm) in case of PCCT and of 8.94 mGy (CTDI16cm) in case of CBCT. The quality of delineation of hard tissues, root-canals, periodontal-space as well as apical osteolysis was assessed by two readers. Mean visibility scores and interrater-agreement (overall agreement (%)) were calculated. Vertical bone loss (bl) and thickness (bt) of the buccal bone lamina of 15 lower incisors were measured and compared to reference measurements by ore microscopy and clinical probing.

Female genital injury-which findings have to be considered physiological using colposcopy with and without toluidine blue dye?

This study aimed to assess the validity and efficacy of blue dye in colposcopic assessment of genital injury in pre- and postmenopausal women with and without history of consensual sexual intercourse. Two hundred women were prospectively enrolled and examined colposcopically with and without toluidine blue dye in order to detect and categorize genital lesions (laceration, bruise and abrasion). Examination of genital trauma was accomplished in a standardized way and findings were photo documented. A wide range of influencing factors with a potential impact on prevalence and nature of genital injury was recorded beforehand using a questionnaire. The frequency of diagnostic injury differed substantially depending on the examination technique, ranging from 9% using colposcopic magnification only to 28% with the additional use of toluidine blue dye. A vertical laceration affecting the posterior fourchette was the most frequent lesion detected (17%, n = 32). Menopausal status seems to have significant impact on genital injury prevalence (p = 0.0165), as 42% (16/ 38) of postmenopausal compared to 24% (36/ 151) of premenopausal women had at least one genital lesion. Furthermore, vaginal medication (p = 0.0369), vaginal dryness (p = 0.0228), dyspareunia (p = 0.0234) and low frequency of sexual intercourse (p = 0.0022) were found to significantly correlate with the presence of genital lesions. According to our findings, standardized colposcopy in combination with toluidine blue dye facilitates accurate assessment of genital lesions. Genital trauma situated at another site than the posterior part of the vaginal introitus seems to be uncommon after consensual intercourse.

Photon-counting normalized metal artifact reduction (NMAR) in diagnostic CT.

PURPOSE: Metal artifacts can drastically reduce the diagnostic value of computed tomography (CT) images. Even the state-of-the-art algorithms cannot remove them completely. Photon-counting CT inherently provides spectral information, similar to dual-energy CT. Many applications, such as material decomposition, are not possible when metal artifacts are present. Our aim is to develop a prior-based metal artifact reduction specifically for photon-counting CT that can correct each bin image individually or in their combinations. METHODS: Photon-counting CT sorts incoming photons into several energy bins, producing bin and threshold images containing spectral information. We use this spectral information to obtain a better prior image for the state-of-the-art metal artifact reduction algorithm FSNMAR. First, we apply a non-linear transformation to the bin images to obtain bone-emphasized images. Subsequently, we forward-project the bin images and bone-emphasized images and multiply the resulting sinograms with each other element-wise to mimic beam hardening effects. These sinograms are reconstructed and linearly combined to produce an artifact-reduced image. The coefficients of this linear combination are automatically determined by minimizing a threshold-based cost function in the image domain. After thresholding, we obtain the prior image for FSNMAR, which is applied to the individual bin images and the lowest threshold image. We test our photon-counting normalized metal artifact reduction (PCNMAR) on forensic CT data and compare it to conventional FSNMAR, where the prior is generated via linear sinogram inpainting. For numerical analysis, we compute both the standard deviation in an ROI with metal artifacts and the CNR of soft tissue and fat. RESULTS: PCNMAR can effectively reduce metal artifacts without sacrificing the overall image quality. Compared to FSNMAR, our method produces fewer secondary artifacts and is more consistent with the measurements. Areas that contain metal, air, and soft tissue are more accurate in PCNMAR. In some cases, the standard deviation in the artifact ROI is reduced by more than 50% relative to FSNMAR, while the CNR values are similar. If extreme artifacts are present, PCNMAR is unable to outperform FSNMAR. Using either two, four, or only the highest energy bin to produce the prior image yielded comparable results. CONCLUSIONS: PCNMAR is an effective method of reducing metal artifacts in photon-counting CT. The spectral information available in photon-counting CT is highly beneficial for metal artifact reduction, especially the high-energy bin, which inherently contains fewer artifacts. While scanning with four instead of two bins does not provide a better artifact reduction, it allows for more freedom in the selection of energy thresholds.

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development.

Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).

Effects of Detector Sampling on Noise Reduction in Clinical Photon-Counting Whole-Body Computed Tomography.

OBJECTIVES: Reconstructing images from measurements with small pixels below the system's resolution limit theoretically results in image noise reduction compared with measurements with larger pixels. We evaluate and quantify this effect using data acquired with the small pixels of a photon-counting (PC) computed tomography scanner that can be operated in different detector pixel binning modes and with a conventional energy-integrating (EI) detector. MATERIALS AND METHODS: An anthropomorphic abdominal phantom that can be extended to 3 sizes by adding fat extension rings, equipped with iodine inserts as well as human cadavers, was measured at tube voltages ranging from 80 to 140 kV. The images were acquired with the EI detector (0.6 mm pixel size at isocenter) and the PC detector operating in Macro mode (0.5 mm pixel size at iso) and ultrahigh-resolution (UHR) mode (0.25 mm pixel size at iso). Both detectors are components of the same dual-source prototype computed tomography system. During reconstruction, the modulation transfer functions were matched to the one of the EI detector. The dose-normalized contrast-to-noise ratio (CNRD) values are evaluated as a figure of merit. RESULTS: Images acquired in UHR mode achieve on average approximately 6% higher CNRD compared with Macro mode at the same spatial resolution for a quantitative D40f kernel. Using a sharper B70f kernel, the improvement increases to 21% on average. In addition, the better performance of PC detectors compared with EI detectors with regard to iodine imaging has been evaluated by comparing CNRD values for Macro and EI. Combining both of these effects, a CNRD improvement of up to 34%, corresponding to a potential dose reduction of up to 43%, can be achieved for D40f. CONCLUSIONS: Reconstruction of UHR data with a modulation transfer function below the system's resolution limit reduces image noise for all patient sizes and tube voltages compared with standard acquisitions. Thus, a relevant dose reduction may be clinically possible while maintaining image quality.

Hippocampal Characteristics and Invariant Sequence Elements Distribution of GLRA2 and GLRA3 C-to-U Editing.

Glycine receptor α2 and α3 subunit (GLRA2/GLRA3) high-affinity variants, of which the subjacent amino acid substitutions issue from C-to-U RNA editing, are thought to influence tonic inhibition and pathophysiology. In light of the detection of GLRA3 NM_006529:r.1157C>U and GLRA2 NM_002063:r.1416C>U exchanges in hippocampus explants of temporal lobe epilepsy patients, we now examine the healthy situation and relate it to the epileptic situation by ascertaining controls in a legitimate reanalysis. The GLRA2 and GLRA3 editing events that would ultimately result in a glycine receptor with increased affinity occur in the postmortem nonepileptic hippocampus. Most notably, their relative amounts do not significantly differ from those in increased damaged hippocampus explants, whereas curbed relative amounts in epileptic explants without cell loss come out statistically significant. Local sequence alignment reveals invariant sequence stretches consistent in GLRA2/ GLRA3 and other edited transcripts that coincide with known APOB sequence elements. Concerning the essential mooring element, GLRA2/GLRA3 comply strictly only with the motif's 5' part. While this lack of canonical mooring elements and uncertain action of the famous deaminase APOBEC1 suggest a specific regulation of GLRA2/GLRA3 editing, its reduction in the less-damaged epileptic hippocampus could be attributed to anomalous epileptic neurogenesis.

[Conventional radiology versus the increasing importance of post-mortem computed tomography]. / Konventionelle Radiologie im Zeitalter (zunehmender Bedeutung) der postmortalen Computertomographie.

Radiological imaging can provide valuable additional information, facilitate and improve the quality of subsequent autopsy. Although the use of cross-sectional imaging methods is increasing, they are not always available in medico-legal practice. In many cases it is advisable to perform conventional X-rays before autopsy, especially in cases of gunshot injuries, as illustrated by a case in which the victim suffered several gunshot wounds with one projectile lodged in a vertebral body. The radiological findings essentially contributed to the rapid location of the projectiles and the reconstruction of the bullet paths.

Health-related quality of life before and during adjuvant interferon-α treatment for patients with malignant melanoma (DeCOG-trial).

Adjuvant treatment with interferon-α (IFN-α) for patients with malignant melanoma can improve relapse-free and overall survival, but IFN-associated side effects may reduce patient's quality of life. The aim of the study was to prospectively evaluate health-related quality of life (HRQoL) in patients with melanoma before and during Low-Dose IFN-α therapy. In a prospective multicenter trial conducted by the Dermatologic Cooperative Oncology Group, 850 patients with cutaneous stage II malignant melanoma received a standard Low-Dose of IFN-α-2a. We evaluated HRQoL using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 questionnaire at baseline and after 3, 6, and 12 months of IFN-α treatment in 282 patients. Nine of 15 subscales showed significant poorer results after 3 months of adjuvant IFN treatment. Symptoms included reduced physical functioning, reduced cognitive functioning, fatigue, nausea, pain, dyspnea, insomnia, diarrhea, and loss of appetite. We did not find a significant change over time for role, emotional, or social functioning. Only cognitive functioning and dyspnea continuously worsened through the twelfth month. At baseline women had significantly lower scores for physical and emotional functioning and for fatigue compared with men. During treatment, women scored significantly poorer on physical functioning, emotional functioning, fatigue, pain, and constipation subscales. Patients who reported having a bad or very bad QoL before treatment were 5.8 times more likely to discontinue treatment early because of psychiatric problems. We conclude that adjuvant low-dose IFN treatment is associated with significant deterioration of HRQoL. Specific psychosocial care should be offered especially for patients who report lower HRQoL and emotional problems before treatment to prevent early discontinuation.

Necrotizing fasciitis with fatal outcome: a report of two cases.

Two cases of sudden and unexpected death due to necrotizing fasciitis are presented with a short overview of this rare disease with special reference to pathological features and causative and epidemiological factors. One case occurred as a complication of liposuction surgery, and the second presented after minor trauma. Based on the autopsy findings and an interdisciplinary approach, medico-legal evaluation provides a substantial basis for later court hearings in such cases.

Depressive mood changes and psychiatric symptoms during 12-month low-dose interferon-alpha treatment in patients with malignant melanoma: results from the multicenter DeCOG trial.

The purpose of the present study was to evaluate the incidence, spectrum and extent of psychiatric symptoms in patients with malignant melanoma (MM) before and during adjuvant treatment with interferon-alpha (IFN-alpha). 850 patients with cutaneous MM of > or =1.5 mm tumor thickness received standard low-dose IFN-alpha 2a in this prospective multicenter trial of the Dermatologic Cooperative Oncology Group (DeCOG). Psychiatric symptoms were evaluated at baseline and after 3, 6, and 12 months with the Beck Depression Inventory (BDI) and the Symptom Check List 90-Revised (SCL 90-R). In all, 282 patients completed all questionnaires. Mean BDI depression scores increased significantly during the first 6 months of IFN-alpha treatment (P < or =0.001), followed by a mild but not significant decrease. Also mean SCL 90-R scores increased significantly during the first 3 months of adjuvant treatment with IFN-alpha (P< or =0.001) and remained elevated until month 12 (P< or =0.001). Only 5% developed BDI scores >10, indicating a clinically significant depressive syndrome and only 1.4% reached a BDI score > or =18, indicating a moderate to severe depressive syndrome. Patients, who dropped-out early from psychiatric reasons, had significantly increased BDI and SCL-90R scores at baseline. Women scored higher in both scales before and during treatment if compared with men. In conclusion, adjuvant treatment with IFN-alpha was associated with a significant increase of BDI- and SCL 90-R scores. A higher pretreatment depression score was found to be a risk factor for an early drop-out during therapy. Pretreatment screening and an interdisciplinary care of the patients is recommended.

Pressure ulcers: a critical review of definitions and classifications.

Pressure ulcers are serious health problems. Although a vast amount of literature addresses prevention and treatment strategies, conceptual difficulties persist regarding pressure ulcer definitions, classifications, and distinction from other tissue lesions. Based on a review of terminologies as well as current state of knowledge on pathophysiology and etiology, questions as to what pressure ulcers are and what they are not are addressed. Because pressure forces seem to play a minor role in the development of superficial ulcers, the authors suggest these types of wounds no longer be termed pressure ulcers. A more general term such as decubitus ulcer may be a more appropriate way to characterize wounds that emerge as a result of compressive forces, shearing forces, and/or friction in patients dependent on skilled care. For clinical practice, a two-category classification is proposed: superficial ulcers predominantly caused by friction and deep ulcers predominantly caused by pressure. This simple classification could enhance diagnostic accuracy and reliability. Multidisciplinary communication and research is needed to develop valid and reliable definitions and classifications for pressure ulcer-like wounds.