Radiomics in diffusion data: a test-retest, inter- and intra-reader DWI phantom study.

AIM: The aim of this study was to evaluate the robustness of radiomics features of a MRI (magnetic resonance imaging) phantom in quantitative diffusion-weighted imaging (DWI) and depending on the image resolution. MATERIALS AND METHODS: Scanning of an in-house developed DWI phantom was performed at a 1.5 T MRI scanner (Magnetom AERA, Siemens, Erlangen, Germany) using an echo planar imaging (EPI) DWI sequence (b=0,500,1,000 s/mm2) with low (3×3 mm2) and high (2×2 mm2) image resolutions. Scans were repeated after phantom repositioning to evaluate retest reliability. Radiomics features were extracted after semi-automatic segmentation and standardised pre-processing. Intra-/interobserver reproducibility and test-retest robustness were assessed using intraclass correlation coefficients (ICC). Differences were tested with non-parametric Wilcoxon's signed-rank and Friedman's test (p < 0.05) with Dunn's post-hoc analysis. RESULTS: Test-retest ICC was overall high with >0.90 for 39/46 radiomics features in all sequences/resolutions. Decreased test-retest ICCs were pronounced for conventional Min-value (overall ICC=0.817), and grey-level zone length matrix (GLZLM) features Short-Zone Emphasis (SZE) and Short-Zone Low Grey-level Emphasis (SZLGE) (for both overall ICC=0.927). Test-retest reproducibility was significantly different between b=500, 1,000 and apparent diffusion coefficient (ADC) (mean 0.975±0.050, 0.974±0.051 and 0.966±0.063), which remained significant after post-hoc analysis between b=1,000 and ADC (p = 0.022). ICCs were not significantly different between resolutions of 2×2 and 3×3 mm2 regarding b=500 (mean: 0.977±0.052 and 0.974±0.049, p = 0.612), b=1,000 (mean: 0.973±0.059 and 0.974±0.054, p = 0.516), and ADC (mean: 0.972±0.049 and 0.955±0.101, p = 0.851). Inter- and intra-observer reliability was consistently high for all sequences (overall mean 0.992±0.021 and 0.990±0.028). CONCLUSION: Under ex-vivo conditions, DWI provided robust radiomics features with those from ADC being slightly less robust than from raw DWI (b=500, 1,000 s/mm2). No significant difference was detected for different resolutions. Although, ex-vivo reliability of DWI radiomics features was high, no implications can be made regarding in-vivo analyses.

Genomic analysis of perinatal sucking reflex in German Brown Swiss calves.

A healthy sucking reflex is essential for newborn calves to ensure sufficient colostrum intake in the first few hours postpartum. In recent decades, European Brown Swiss breeders have repeatedly reported that some calves lack the ability to consume colostrum directly after birth due to an absent sucking reflex. In this study, we collected the phenotypes of more than 5,500 German Brown Swiss calves and performed variance component estimation with sire threshold models using Markov chain Monte Carlo algorithms. The 50K (777K) genotypes of nearly 2,000 (200) calves were collected, and an imputation was performed for all 50K genotypes up to 777K. Genome-wide association studies (GWAS) for the trait sucking reflex were conducted for all 777K genotypes. Depending on the trait coding, a low heritability was estimated to range from 0.08 to 0.11. The GWAS results identified 34 trait-associated SNP on 6 different chromosomes. Post-GWAS analyses showed significant overrepresentation of Gene Ontologies for central nervous development and several regulative processes. Functional annotation clustering and pathway analysis revealed relations to lipid metabolism, immune and endocrine systems, and signal transduction. The results of this study suggest that breeding for an improved sucking reflex is possible but requires large data sets for the estimation of reliable breeding values (either large progeny testing groups or a large reference genome in a genomic selection program).

[Diffusion-weighted imaging-diagnostic supplement or alternative to contrast agents in early detection of malignancies?] / Diffusionsbildgebung ­ diagnostische Erweiterung oder Ersatz von Kontrastmitteln in der Früherkennung von Malignomen?

Medical research in the field of oncologic imaging diagnostics using magnetic resonance imaging increasingly includes diffusion-weighted imaging (DWI) sequences. The DWI sequences allow insights into different microstructural diffusion properties of water molecules in tissues depending on the sequence modification used and enable visual and quantitative analysis of the acquired imaging data. In DWI, the application of intravenous gadolinium-containing contrast agents is unnecessary and only the mobility of naturally occurring water molecules in tissues is quantified. These characteristics predispose DWI as a potential candidate for emerging as an independent diagnostic tool in selected cases and specific points in question. Current clinical diagnostic studies and the ongoing technical developments, including the increasing influence of artificial intelligence in radiology, support the growing importance of DWI. Especially with respect to selective approaches for early detection of malignancies, DWI could make an essential contribution as an eligible diagnostic tool; however, prior to discussing a broader clinical implementation, challenges regarding reliable data quality, standardization and quality assurance must be overcome.

Diffusion-weighted breast imaging.

Magnetic resonance imaging (MRI) of the breast represents one of the most sensitive imaging modalities in breast cancer detection. Diffusion-weighted imaging (DWI) is a sequence variation introduced as a complementary MRI technique that relies on mapping the diffusion process of water molecules thereby providing additional information about the underlying tissue. Since water diffusion is more restricted in most malignant tumors than in benign ones owing to the higher cellularity of the rapidly proliferating neoplasia, DWI has the potential to contribute to the identification and characterization of suspicious breast lesions. Thus, DWI might increase the diagnostic accuracy of breast MRI and its clinical value. Future applications including optimized DWI sequences, technical developments in MR devices, and the application of radiomics/artificial intelligence algorithms may expand the potential of DWI in breast imaging beyond its current supplementary role.

MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI.

BACKGROUND: To date, only limited magnetic resonance imaging (MRI) data are available concerning tumor regression during neoadjuvant radiochemotherapy (RCT) of rectal cancer patients, which is a prerequisite for adaptive radiotherapy (RT) concepts. This exploratory study prospectively evaluated daily fractional MRI during neoadjuvant treatment to analyze the predictive value of MR biomarkers for treatment response. METHODS: Locally advanced rectal cancer patients were examined with daily MRI during neoadjuvant RCT. Contouring of the tumor volume was performed for each MRI scan by using T2- and diffusion-weighted-imaging (DWI)-sequences. The daily apparent-diffusion coefficient (ADC) was calculated. Volumetric and functional tumor changes during RCT were analyzed and correlated with the pathological response after surgical resection. RESULTS: In total, 171 MRI scans of eight patients were analyzed regarding anatomical and functional dynamics during RCT. Pathological complete response (pCR) could be achieved in four patients, and four patients had a pathological partial response (pPR) following neoadjuvant treatment. T2- and DWI-based volumetry proved to be statistically significant in terms of therapeutic response, and volumetric thresholds at week two and week four during RCT were defined for the prediction of pCR. In contrast, the average tumor ADC values widely overlapped between both response groups during RCT and appeared inadequate to predict treatment response in our patient cohort. CONCLUSION: This prospective exploratory study supports the hypothesis that MRI may be able to predict pCR of rectal cancers early during neoadjuvant RCT. Our data therefore provide a useful template to tailor future MR-guided adaptive treatment concepts.

Expression of the proliferation-associated Ki-67 antigen of transferrin receptors and of DNA polymerase alpha in human tumour lines: implications for in vitro chemoresistance.

To compare the time course of in vitro expression of various proliferation-associated markers including Ki-67 antigen, transferrin receptors (TfR), and DNA polymerase alpha, six human tumour cell lines of different histological origin were studied under defined conditions. Proliferation markers were demonstrated by peroxidase/anti-peroxidase staining using specific monoclonal antibodies, and their expression was compared to results obtained from [3H]-thymidine incorporation assays and cell counting. Expression of all proliferation markers began to increase during the lag phase, and occurred earlier than elevations of [3H]dT incorporation and cell numbers were recorded. Maximum expression was observed before cell growth reached plateau phase. The time courses of expression of DNA polymerase and Ki-67 were almost identical. The closest correlation of [3H]dT incorporation with time course of expression of proliferation-associated markers was observed, when intranuclear staining of DNA polymerase was analysed. TfR were expressed earlier than the polymerase and Ki-67. Since TfR were also found at remarkable levels in resting cells, they seem less proliferation-specific than Ki-67 and DNA polymerase. While in rapidly growing cell lines more than 95% of the cells expressed Ki-67, TfR, and more than 75% DNA polymerase in cell nuclei, a malignant melanoma and a pleural mesothelioma line displayed fewer than 35% of cells stained for DNA polymerase in cell nuclei during log phase. Determination of growth fractions by monoclonal antibodies may thus contribute to the prediction of chemoresistance by identifying quiescent cells that are not sensitive to S-phase-specific drugs.

Starch digestibility of foods: a nutritional perspective.

Dietary starch varies greatly in digestibility and its effects on the utilization of other nutrients. The variation appears to be due to differences in starch components and their crystallinity. Processing treatments, storage conditions, chemical modification, and genetic breeding influence the digestibility of starch. Cereal starches are generally more digestible than root/tuber and legume starches. Although cooking often significantly improves the digestibility of poor and intermediately digestible starches, some foods such as bananas with starches of these types are consumed uncooked. The efficient digestion of starch is especially important to specific groups of people such as infants under 6 months of age. Ruminants must also be provided with highly digestible starch to assure maximum production efficiency. Poor digestibility of starch may have negative effects on the utilization of protein and minerals but is likely to have positive effects on the availability of certain vitamins. Decreases in the rate of starch digestion may have therapeutic application. Most clinical studies have reported that starch blockers do not elicit a significant decrease in the digestion of starch in humans. Much remains to be learned, clarified, and understood about starch digestion and its effects on diabetes and weight control.