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Abstract Objective The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.

The chicken embryo has emerged as a valuable model for preclinical studies due to its unique combination of accessibility, affordability, and relevance to human biology. Its rapid development, external growth environment, and clear structural visibility offer distinct advantages over traditional mammalian models. These features facilitate the study of real-time biological processes, including tissue development, tumor growth, angiogenesis, and drug delivery, using various imaging modalities, such as optical imaging, magnetic resonance imaging, positron emission tomography, computed tomography, and ultrasound. The chicken embryo model also minimizes ethical concerns compared to mammalian models, as it allows for early-stage research without the complexity of a fully developed animal. Moreover, its ability to integrate human tumor cells into xenograft models provides a reliable platform for cancer research, enabling high-throughput screening of therapeutic interventions and tracking molecular dynamics in vivo. Advances in molecular imaging techniques further enhance the resolution and depth of data obtained from these studies, offering insights into cellular and molecular mechanisms underlying disease. Given its versatility, cost-effectiveness, and translational potential, the chicken embryo represents a promising tool for advancing preclinical research, particularly in drug development, cancer biology, and regenerative medicine.

Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman’s correlation (ρ). Before–after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients.

The chicken embryo has emerged as a valuable model for preclinical studies due to its unique combination of accessibility, affordability, and relevance to human biology. Its rapid development, external growth environment, and clear structural visibility offer distinct advantages over traditional mammalian models. These features facilitate the study of real-time biological processes, including tissue development, tumor growth, angiogenesis, and drug delivery, using various imaging modalities, such as optical imaging, magnetic resonance imaging, positron emission tomography, computed tomography, and ultrasound. The chicken embryo model also minimizes ethical concerns compared to mammalian models, as it allows for early-stage research without the complexity of a fully developed animal. Moreover, its ability to integrate human tumor cells into xenograft models provides a reliable platform for cancer research, enabling high-throughput screening of therapeutic interventions and tracking molecular dynamics in vivo. Advances in molecular imaging techniques further enhance the resolution and depth of data obtained from these studies, offering insights into cellular and molecular mechanisms underlying disease. Given its versatility, cost-effectiveness, and translational potential, the chicken embryo represents a promising tool for advancing preclinical research, particularly in drug development, cancer biology, and regenerative medicine. [ABSTRACT FROM AUTHOR]

Objective: The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex. [ABSTRACT FROM AUTHOR]

Over the past decade, medical imaging technologies have become increasingly significant in both clinical and preclinical research, leading to a better understanding of disease processes and the development of new diagnostic and theranostic methods. Radiomic and radiogenomic approaches have furthered this progress by exploring the relationship between imaging characteristics, genomic information, and outcomes that qualitative interpretations may have overlooked, offering valuable insights for personalized medicine. Preclinical research allows for a controlled environment where various aspects of a pathology can be replicated in animal models, providing radiomic and radiogenomic approaches with the unique opportunity to investigate the causal connection between imaging and molecular factors. The aim of this review is to present the current state of the art in the application of radiomics and radiogenomics on murine models. This review will provide a brief description of relevant articles found in the literature with a discussion on the implications and potential translational relevance of these findings. [ABSTRACT FROM AUTHOR]

Background: Oligometastatic disease (OMD) represents an indolent cancer status characterized by slow tumor growth and limited metastatic potential. The use of local therapy in the management of the condition continues to rise. This study aimed to investigate the advantage of pretreatment tumor growth rate in addition to baseline disease burden in characterizing OMDs, generally defined by the presence of ≤ 5 metastatic lesions. Methods: The study included patients with metastatic melanoma treated with pembrolizumab. Gross tumor volume of all metastases was contoured on imaging before (TP-1) and at the initiation of pembrolizumab (TP0). Pretreatment tumor growth rate was calculated by an exponential ordinary differential equation model using the sum of tumor volumes at TP-1 and TP0 and the time interval between TP-1. and TP0. Patients were divided into interquartile groups based on pretreatment growth rate. Overall survival, progression-free survival, and subsequent progression-free survival were the study outcomes. Results: At baseline, median cumulative volume and number of metastases were 28.4 cc (range, 0.4-1194.8 cc) and 7 (range, 1-73), respectively. The median interval between TP-1 and TP0 was -90 days and pretreatment tumor growth rate (×10-2 days-1) was median 4.71 (range -0.62 to 44.1). The slow-paced group (pretreatment tumor growth rate ≤ 7.6 ×10-2 days-1, the upper quartile) had a significantly higher overall survival rate, progression-free survival, and subsequent progression-free survival compared to those of the fast-paced group (pretreatment tumor growth rate > 7.6 ×10-2 days-1). Notably, these differences were prominent in the subgroup with >5 metastases. Conclusion: Pretreatment tumor growth rate is a novel prognostic metric associated with overall survival, progression-free survival, and subsequent progression-free survival among metastatic melanoma patients, especially patients with >5 metastases. Future prospective studies should validate the advantage of disease growth rate plus disease burden in better defining OMDs. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Clinical correlates of R1 relaxometry and magnetic susceptibility changes in multiple sclerosis: a multi-parameter quantitative MRI study of brain iron and myelin" published in December 8, 2022 issue.

Objectives: The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS. Methods: In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons. Results: MS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04). Conclusions: We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition. Key Points: • Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus. • Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy. • Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation. [ABSTRACT FROM AUTHOR]

The ratio of T1-weighted/T2-weighted magnetic resonance images (T1w/T2w MRI) has been successfully applied at the cortical level since 2011 and is now one of the most used myelin mapping methods. However, no reports have explored the histological validity of T1w/T2w myelin mapping in white matter. Here we compare T1w/T2w with ex vivo postmortem histology and in vivo MRI methods, namely quantitative susceptibility mapping (QSM) and multi-echo T2 myelin water fraction (MWF) mapping techniques. We report a discrepancy between T1w/T2w myelin maps of the human corpus callosum and the histology and analyse the putative causes behind such discrepancy. T1w/T2w does not positively correlate with Luxol Fast Blue (LFB)-Optical Density but shows a weak to moderate, yet significant, negative correlation. On the contrary, MWF is strongly and positively correlated with LFB, whereas T1w/T2w and MWF maps are weakly negatively correlated. The discrepancy between T1w/T2w MRI maps, MWF and histological myelin maps suggests caution in using T1w/T2w as a white matter mapping method at the callosal level. While T1w/T2w imaging may correlate with myelin content at the cortical level, it is not a specific method to map myelin density in white matter. [ABSTRACT FROM AUTHOR]

Objective: To explore the feasibility of using a contrast-enhanced CT image-based radiomics model to predict central cervical lymph node status in patients with thyroid nodules. Methods: Pretreatment clinical and CT imaging data from 271 patients with surgically diagnosed and treated thyroid nodules were retrospectively analyzed. According to the pathological features of the thyroid nodules and central lymph nodes, the patients were divided into three groups: group 1: papillary thyroid carcinoma (PTC) metastatic lymph node group; group 2: PTC nonmetastatic lymph node group; and group 3: benign thyroid nodule reactive lymph node group. Radiomics models were constructed to compare the three groups by pairwise classification (model 1: group 1 vs group 3; model 2: group 1 vs group 2; model 3: group 2 vs group 3; andmodel 4: group 1 vs groups (2 + 3)). The feature parameters with good generalizability and clinical risk factors were screened. A nomogram was constructed by combining the radiomics features and clinical risk factors. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were performed to assess the diagnostic and clinical value of the nomogram. Results: For radiomics models 1, 2, and 3, the areas under the curve (AUCs) in the training group were 0.97, 0.96, and 0.93, respectively. The following independent clinical risk factors were identified: model 1, arterial phase CT values; model 2, sex and arterial phase CT values; model 3: none. The AUCs for the nomograms of models 1 and 2 in the training group were 0.98 and 0.97, respectively, and those in the test group were 0.95 and 0.87, respectively. The AUCs of the model 4 nomogram in the training and test groups were 0.96 and 0.94, respectively. Calibration curve analysis and DCA revealed the high clinical value of the nomograms of models 1, 2 and 4. Conclusion: The nomograms based on contrast-enhanced CT images had good predictive efficacy in classifying benign and malignant central cervical lymph nodes of thyroid nodule patients. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is an important modality in cancer treatment with >50% of cancer patients undergoing RT for curative or palliative intent. In patients with breast, lung, and esophageal cancer, as well as mediastinal malignancies, incidental RT dose to heart or vascular structures has been linked to the development of Radiation-Induced Heart Disease (RIHD) which manifests as ischemic heart disease, cardiomyopathy, cardiac dysfunction, and heart failure. Despite the remarkable progress in the delivery of radiotherapy treatment, offtarget cardiac toxicities are unavoidable. One of the best-studied pathological consequences of incidental exposure of the heart to RT is collagen deposition and fibrosis, leading to the development of radiation-induced myocardial fibrosis (RIMF). However, the pathogenesis of RIMF is still largely unknown. Moreover, there are no available clinical approaches to reverse RIMF once it occurs and it continues to impair the quality of life of long-term cancer survivors. Hence, there is an increasing need for more clinically relevant preclinical models to elucidate the molecular and cellular mechanisms involved in the development of RIMF. This review offers an insight into the existing preclinical models to study RIHD and the suggested mechanisms of RIMF, as well as available multi-modality treatments and outcomes. Moreover, we summarize the valuable detection methods of RIHD/RIMF, and the clinical use of sensitive radiographic and circulating biomarkers. [ABSTRACT FROM AUTHOR]

Objectives: Although the use of specific MRI criteria has significantly increased the diagnostic accuracy of multiple sclerosis (MS), reaching a correct neuroradiological diagnosis remains a challenging task, and therefore the search for new imaging biomarkers is crucial. This study aims to evaluate the incidence of one of the emerging neuroradiological signs highly suggestive of MS, the central vein sign (CVS), using data from Fabry disease (FD) patients as an index of microvascular disorder that could mimic MS. Methods: In this retrospective study, after the application of inclusion and exclusion criteria, MRI scans of 36 FD patients and 73 relapsing–remitting (RR) MS patients were evaluated. Among the RRMS participants, 32 subjects with a disease duration inferior to 5 years (early MS) were also analyzed. For all subjects, a Fazekas score (FS) was recorded, excluding patients with FS = 0. Different neuroradiological signs, including CVS, were evaluated on FLAIR T2-weighted and spoiled gradient recalled echo sequences. Results: Among all the recorded neuroradiological signs, the most striking difference was found for the CVS, with a detectable prevalence of 78.1% (57/73) in RRMS and of 71.4% (25/32) in early MS patients, while this sign was absent in FD (0/36). Conclusions: Our results confirm the high incidence of CVS in MS, also in the early phases of the disease, while it seems to be absent in conditions with a different etiology. These results corroborate the possible role of CVS as a useful neuroradiological sign highly suggestive of MS. Key Points: • The search for new imaging biomarkers is crucial to achieve a correct neuroradiological diagnosis of MS. • The CVS shows an incidence superior to 70% in MS patients, even in the early phases of the disease, while it appears to be absent in FD. • These findings further corroborate the possible future central role of CVS in distinguishing between MS and its mimickers. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-induced esophagitis (RE) is a common dose-limiting complication associated with concurrent chemoradiation therapy for Non-Small-Cell Lung Cancer (NSCLC), and a wide range of esophageal dosimetric parameters have been described as predictive of RE. In this study, we characterize the risk of RE for NSCLC patients enrolled in a prospective trial comparing intensity-modulated RT versus passive scattering proton therapy for locally advanced NSCLC. Dose patterns associated with RE were analyzed by applying voxel-based analysis approaches, and predictive models for RE were finally investigated. Two predictive models for acute RE with good cross-validated predictive performances and discrimination capability were developed (thoracic esophageal model: ROC-AUC = 0.73; whole esophagus model: ROC-AUC = 0.70). The aim of our study is to characterize the risk of radiation-induced esophagitis (RE) in a cohort of Non-Small-Cell Lung Cancer (NSCLC) patients treated with concurrent chemotherapy and photon/proton therapy. For each patient, the RE was graded according to the CTCAE v.3. The esophageal dose-volume histograms (DVHs) were extracted. Voxel-based analyses (VBAs) were performed to assess the spatial patterns of the dose differences between patients with and without RE of grade ≥ 2. Two hierarchical NTCP models were developed by multivariable stepwise logistic regression based on non-dosimetric factors and on the DVH metrics for the whole esophagus and its anatomical subsites identified by the VBA. In the 173 analyzed patients, 76 (44%) developed RE of grade ≥ 2 at a median follow-up time of 31 days. The VBA identified regions of significant association between dose and RE in a region encompassing the thoracic esophagus. We developed two NTCP models, including the RT modality and a dosimetric factor: V55Gy for the model related to the whole esophagus, and the mean dose for the model designed on the thoracic esophagus. The cross-validated performance showed good predictions for both models (ROC-AUC of 0.70 and 0.73, respectively). The only slight improvement provided by the analysis of the thoracic esophageal subsites might be due to the relevant sparing of cervical and lower thoracic esophagus in the analyzed cohort. Further studies on larger cohorts and a more heterogeneous set of dose distributions are needed to validate these preliminary findings and shed further light on the spatial patterns of RE development. [ABSTRACT FROM AUTHOR]

Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman's correlation (ρ). Before–after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients. [ABSTRACT FROM AUTHOR]