Radiogenomics and Texture Analysis to Detect von Hippel-Lindau (VHL) Mutation in Clear Cell Renal Cell Carcinoma.

Radiogenomics, a burgeoning field in biomedical research, explores the correlation between imaging features and genomic data, aiming to link macroscopic manifestations with molecular characteristics. In this review, we examine existing radiogenomics literature in clear cell renal cell carcinoma (ccRCC), the predominant renal cancer, and von Hippel-Lindau (VHL) gene mutation, the most frequent genetic mutation in ccRCC. A thorough examination of the literature was conducted through searches on the PubMed, Medline, Cochrane Library, Google Scholar, and Web of Science databases. Inclusion criteria encompassed articles published in English between 2014 and 2022, resulting in 10 articles meeting the criteria out of 39 initially retrieved articles. Most of these studies applied computed tomography (CT) images obtained from open source and institutional databases. This literature review investigates the role of radiogenomics, with and without texture analysis, in predicting VHL gene mutation in ccRCC patients. Radiogenomics leverages imaging modalities such as CT and magnetic resonance imaging (MRI), to analyze macroscopic features and establish connections with molecular elements, providing insights into tumor heterogeneity and biological behavior. The investigations explored diverse mutations, with a specific focus on VHL mutation, and applied CT imaging features for radiogenomic analysis. Moreover, radiomics and machine learning techniques were employed to predict VHL gene mutations based on CT features, demonstrating promising results. Additional studies delved into the relationship between VHL mutation and body composition, revealing significant associations with adipose tissue distribution. The review concludes by highlighting the potential role of radiogenomics in guiding targeted and selective therapies.

Sarcopenia does not impact the outcome of patients with Multiple Mieloma consolidated with autologous Hematopoietic Stem Cell Transplantation.

Sarcopenia has been associated with chronic diseases and cancer. Aim of this study was to evaluate sarcopenia in Multiple Myeloma patients undergoing autologous stem cell trans-plantation. In 68 eligible patients' measurement of skeletal muscle area (cm2) on computed tomography scans at the level of the L3 vertebra (L3-SMI) was performed. 37(54%) patients were categorized as sarcopenic: 26 males with L3-SMI values < 52.4 cm2/m2, and 11 women with L3-SMI values < 38.9 cm2/m2. The majority of sarcopenic patients included were older than 60 years (69%, p=0.0005), and with BMI <25 (75%; p=0.0000). A significant association was found between sarcopenia and Sorror score value > 1 (p=0.02). The Kaplan Meyer curve showed a median OS of 73.5 months for non-sarcopenic patients vs. 86.5 months for sarcopenic patients, suggesting that sarcopenia is not an independent prognostic factor in this cohort of patients.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

Cerebral vasomotor reactivity in the acute phase and after 6 months in non-disabling stroke/TIA: A prospective cohort study.

BACKGROUND AND AIM: Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes in patients with acute non-disabling stroke/Transient Ischemic Attack (TIA) to understand its implication in stroke ethiopatogenesis. METHODS: VMR by Transcranial Doppler Breath Holding test was performed at 48-72 h from stroke onset (T1) and after 6 months (T2) on MCA of the non-affected hemisphere and PCA of the affected hemisphere. RESULTS: We consecutively enrolled 124 patients with a median age of 66.0 (IQR 54.75-74.25) years with a median NIHSS 2 (IQR 1-3). Both MCA (1.38 %/s SD 0.58) and PCA (1.35 %/s SD 0.75) BHI at T1 did not differ among different stroke subtypes (p=0.067 and p=0.350; N=124). MCA and PCA BHI decreased from T1 to T2 (respectively 1.39 %/s SD 0.56 vs 1.18%/s SD 0.44 and 1.30 %/s SD 0.69 vs 1.20 %/s SD 0.51; N=109) regardless of ethiopatogenesis (respectively p<0.0001 and p=0.111). CONCLUSION: The VMR is higher in acute phase than at 6 months in patients with non-disabling stroke/TIA, regardless of etiopathogenesis. The higher VMR in acute phase could be sustained by an increased Cerebral Blood Flow due to collateral circulation activation supporting the ischemic zone.

Deep brain stimulation of the dentato-rubro-thalamic tract in a case of Holmes tremor: a constrained spherical deconvolution (CSD)-guided procedure.

Deep brain stimulation (DBS) is an established treatment for movement disorders, including Holmes tremor (HT). HT is a rest and action tremor that occurs as a late symptom of brainstem lesions such as stroke. Unfortunately, it is frequently refractory to medical treatment, hence DBS surgery may be a good option. Due to variable results, the ideal target for DBS in HT still remains to be established, ranging from the thalamus to the globus pallidus internus, to the subthalamic nucleus. Pre-operative imaging also is very challenging, as the complexity of brain fiber architecture may prevent the correct positioning of the directional lead. Herein, we describe the case of a patient affected by a rubral tremor secondary to a brain hemorrhage, who had advanced pre-operative neuroimaging with constrained spherical deconvolution (CSD)-based tractography obtained from diffusion-weighted imaging (DWI) to identify the dentato-rubro-thalamic tract, involved in the pathophysiology of HT. The patient was then addressed to an awake DBS surgery, and with the help of intraoperative microelectrode recordings, a tailored DRTT-targeted procedure was performed. The stimulation determined an almost complete tremor suppression, with no significant side effects at a follow-up of 6 months, paving the way towards new effective techniques for the planning, i.e., CSD-based tractography and the treatment of refractory tremors.

Complications after abdominal surgery and breast implant pelvic positioning: case report and literature review.

The recommended treatment for patients with locally advanced colorectal cancer (CRC) or other pelvic neoplasms often comprises extensive abdominal surgery and radiation therapy (RT). The major complications of these treatments are radiation enteritis and empty pelvis syndrome, which is the displacement of bowel loops in the pelvic dead space created after the intervention. To avoid these complications, diverse methods of pelvic floor reconstruction have been attempted, one of them being the silicon breast prosthesis pelvic placement. Since literature is scarce on complications secondary to breast implant placement in the pelvis, we consider our case an unusual presentation of this entity offering the availability of novel information.

Relationship between visceral adipose tissue and genetic mutations (VHL and KDM5C) in clear cell renal cell carcinoma.

BACKGROUND: The sequencing of the renal cell carcinoma (RCC) genome has detected several mutations with prognostic meaning. The association between visceral adipose tissue (VAT) and clear cell renal cell carcinoma (ccRCC) is well known. The relationship among abdominal adipose tissue distribution and ccRCC-VHL and KDM5C genetic mutations is, to the knowledge of the authors, not known. METHODS: In this retrospective study, we enrolled 97 Caucasian male patients divided into three groups: the control group (n = 35), the ccRCC-VHL group (n = 52) composed of ccRCC patients with VHL mutations and ccRCC-KDM5C group (n = 10) composed of ccRCC patients with KDM5C mutation. Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in the groups. VAT/SAT ratio was calculated for each subject. RESULTS: Statistically significant differences between ccRCC-KDM5C group and ccRCC-VHL group were obtained for TAT area (p < 0.05), VAT area (p < 0.05) and VAT/SAT ratio (p < 0.05); between ccRCC-VHL group and control group for TAT area (p < 0.001) and VAT area (p < 0.01); and between ccRCC-KDM5C group and control group for TAT area (p < 0.0001), VAT area (p < 0.0001) and SAT area (p < 0.01). CONCLUSIONS: This study demonstrates for the first time an increased amount of TAT, especially VAT, in the ccRCC-VHL and ccRCC-KDM5C groups. The effect was greater for the ccRCC-KDM5C group.

Increased visceral adipose tissue in male patients with non-clear cell renal cell carcinoma.

BACKGROUND: It is well known that there is a link between obesity and oncogenesis in many sites, including the kidney. Adiposopathy is characterized by an excessive accumulation of adipose tissue, principally visceral, which can lead to adipocyte and adipose tissue-related disorder, promoting metabolic syndrome. Visceral adipocytes secrete growth factors, proinflammatory cytokines and adipokines, regarded as mediating factors associated with the oncogenesis of obesity-related tumors. In this study, we evaluate the relationship between visceral adipose tissue (VAT) and non-clear cell renal cell carcinoma (nccRCC) in male patients. METHODS: In this retrospective study, two groups were included: nccRCC group and control group. Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in both groups. VAT/SAT ratio was subsequently calculated. RESULTS: Statistically significant differences between the two groups were found in TAT area (p = 0.05), VAT area (p < 0.01) and VAT/SAT ratio (p < 0.05), while no significant difference was found in SAT area. CONCLUSIONS: This study demonstrates an increased visceral adipose tissue in male patients with nccRCC.

Inverse spatial distribution of brain metastases and white matter hyperintensities in advanced lung and non-lung cancer patients.

The aim of this study was to test by means of a voxel-based approach the hypothesis that there is a different spatial distribution of brain metastases (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects the location of BM in lung and non-lung cancer patients. Two-hundred consecutive cancer patients at first diagnosis of BM were included. Images were acquired using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were post-processed for segmentation, co-registration and analysis. Binary lesion masks were created for WMH and BM, using Volumes of Interest. Lesion probability maps were generated and the voxel-based lesion-symptom mapping approach was used to model each voxel and to calculate a non parametric statistics (Brunner-Munzel test) describing the differences between the groups. In the lung cancer group we found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe and the cerebellum. In contrast, BM were more frequent in the right frontal lobe in WMH+ than in WMH- patients. We suggest that there exists an inverse brain spatial distribution between WMH and BM. In lung cancer patients, the presence of WMH seems to shift the distribution of BM toward locations different than what it is expected based on primary tumor.

Bilateral remote cerebellar haemorrhage after spinal surgery: a case study and review of the literature.

BACKGROUND: Remote cerebellar haemorrhage is a rare and unpredictable complication after intracranial and spinal surgery, although less frequently found in the latter. The physiopathology of this phenomenon has not been definitely explained. OBJECTIVES: To describe and discuss the potential implications and pathomechanism of a bilateral remote cerebellar haemorrhage case after spinal surgery and review the literature related to this rare phenomenon. CASE REPORT: A 75 year-old man developed bilateral remote cerebellar haemorrhage after a lumbar laminectomy. Brain CT and MRI examinations showed chronic bilateral remote cerebellar haemorrhage, right haemoventricle and bilateral supratentorial subarachnoid haemorrhage. Subsequently, the patient underwent rehabilitation therapy with improvement of symptoms. CONCLUSION: When large cerebrospinal fluid loss is observed during spinal surgery, brain imaging study should be carried out. The pathogenetic hypothesis of microcirculation vessels tearing, the role of previous spinal surgery and of cerebellar atrophy should be considered and validated with further investigation.

Temporal Bone High Resolution Computed Tomography Findings in a Case of Postpartum Otosclerosis.

We describe temporal bone high resolution computed tomography (HRCT) findings in a case of bilateral mixed fenestral and retrofenestral otosclerosis with onset in the postpartum period. This condition should be considered in women complaining of postpartum hearing loss and temporal bone HRCT is a fundamental tool leading to the diagnosis.

The sensitivity of MIPs of 3D contrast-enhanced VIBE T1-weighted imaging for the detection of small brain metastases (≤ 5 mm) on 1.5 tesla MRI.

OBJECTIVES: To evaluate whether the use of Maximum Intensity Projection (MIP) images derived from contrast-enhanced 3D-T1-weighted volumetric interpolated breath-hold examination (VIBE) would allow more sensitive detection of small (≤5 mm) brain metastases (BM) compared with source as well as 2D-T1-weighted spin-echo (SE) images. METHODS: We performed a single center retrospective study on subjects with BM who underwent 1.5 tesla brain magnetic resonance imaging. Two readers counted the number of small BM for each of the seven sets of contrast-enhanced images created: axial 2D-T1-weighted SE, 3D-T1-weighted VIBE, 2.5 mm-thick-MIP T1-weighted VIBE, and 5 mm-thick-MIP T1-weighted VIBE; sagittal 3D-T1-weighted VIBE, 2.5 mm-thick-MIP T1-weighted VIBE, and 5 mm-thick-MIP T1-weighted VIBE. Total number of lesions detected on each image type was compared. Sensitivity, the average rates of false negatives and false positives, and the mean discrepancy were evaluated. RESULTS: A total of 403 small BM were identified in 49 patients. Significant differences were found: in the number of true positives and false negatives between the axial 2D-T1-weighted SE sequence and all other imaging techniques; in the number of false positives between the axial 2D-T1-weighted SE and the axial 3D-T1-weighted VIBE sequences. The two image types that combined offered the highest sensitivity were 2D-T1-weighted SE and axial 2.5 mm-thick-MIP T1-weighted VIBE. The axial 2D-T1-weighted SE sequence differed significantly in sensitivity from all other sequences. CONCLUSION: MIP images did not show a significant difference in sensitivity for the detection of small BM compared with native images.

Advancements in Radiogenomics for Clear Cell Renal Cell Carcinoma: Understanding the Impact of BAP1 Mutation.

Recent advancements in understanding clear cell renal cell carcinoma (ccRCC) have underscored the critical role of the BAP1 gene in its pathogenesis and prognosis. While the von Hippel-Lindau (VHL) mutation has been extensively studied, emerging evidence suggests that mutations in BAP1 and other genes significantly impact patient outcomes. Radiogenomics with and without texture analysis based on CT imaging holds promise in predicting BAP1 mutation status and overall survival outcomes. However, prospective studies with larger cohorts and standardized imaging protocols are needed to validate these findings and translate them into clinical practice effectively, paving the way for personalized treatment strategies in ccRCC. This review aims to summarize the current knowledge on the role of BAP1 mutation in ccRCC pathogenesis and prognosis, as well as the potential of radiogenomics in predicting mutation status and clinical outcomes.

Visceral Adiposity and Its Impact on Nephrolithiasis: A Narrative Review.

Kidney stones represent a serious medical problem, resulting from several factors such as diet, genetics, and certain medical conditions. Visceral adipose tissue has been shown in recent research to play a significant role in kidney stone formation, making it a more precise indicator than traditional obesity indicators such as body mass index. The main aim of this review is to summarize studies on visceral obesity as a predictive marker for nephrolithiasis and to highlight new mechanistic pathways such as adipokine-mediated inflammation and its impact on kidney stone formation. This review emphasizes the importance of considering visceral fat in the prevention and management of kidney stones, suggesting that targeted strategies to reduce visceral fat could decrease the incidence of kidney stones and their management costs. Further prospective studies are needed to validate these findings and propose preventive strategies based on visceral adiposity assessments.

Magnetic Resonance Imaging in Uremic Encephalopathy: Identifying Key Imaging Patterns and Clinical Correlations.

Background/Objectives: Magnetic Resonance Imaging (MRI) is essential in diagnosing neurological conditions, offering detailed insights into brain pathology. Uremic encephalopathy (UE) is a severe neurological disorder resulting from renal failure, characterized by cognitive impairments and brain abnormalities due to the accumulation of uremic toxins (UTs). Despite extensive research on UTs, there is a significant gap in the detailed characterization of MRI findings in UE patients. This study aims to bridge this gap by conducting a comprehensive literature review of cerebral MRI findings in UE. We hypothesize that specific MRI patterns correlate with the severity and clinical manifestations of UE, thereby enhancing diagnostic accuracy and improving patient outcomes. Methods: A literature review was performed using PubMed, Cochrane Library, and Google Scholar. The search terms included "uremic encephalopathy MRI", "uremia and kidney failure MRI", and "toxic and metabolic or acquired encephalopathies MRI". The inclusion criteria were original articles on UE and MRI findings published in English. Results: Common MRI sequences include T1-weighted, T2-weighted, FLAIR, and DWI. Frequent MRI findings in UE are cytotoxic and vasogenic brain edema in regions such as the basal ganglia and periventricular white matter. Patterns like the "lentiform fork sign" and basal ganglia involvement are key indicators of UE. Conclusions: MRI plays a crucial role in diagnosing UE by identifying characteristic brain edema and specific patterns. A comprehensive diagnostic approach, incorporating clinical, laboratory, and imaging data, is essential for accurate diagnosis and management. The study calls for larger well-designed cohorts with long-term follow-up to improve the understanding and treatment of UE.

Exploring the ADAM12 Expression in Clear Cell Renal Cell Carcinoma: A Radiogenomic Analysis on CT Imaging.

RATIONALE AND OBJECTIVES: Radiogenomics of clear cell renal cell carcinoma (ccRCC) has been developed thanks to the availability of genomic data, both gene expressions and gene mutations, obtained through the sequencing of ccRCC genome. These data are collected in the Cancer Genome Atlas (TCGA) Research Network-work. Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) gene belongs to the family of genes coding for multidomain and multifunctional type I transmembrane proteins ADAMs. These proteins are fundamental for regulating cell adhesion and mediating proteolysis of a series of cell surface receptors and signal molecules extracellular domains. Recently, a correlation was detected between ADAM12 expression in ccRCC and tumor aggressiveness in terms of cell proliferation, migration, invasion, tumor progression, metastases, and poor prognosis, suggesting ADAM12 as a prognostic marker and therapeutic target in ccRCC. The computed tomography (CT) imaging phenotype of ADAM12 expression in ccRCC has never been studied. The aim of this study is to investigate the CT imaging phenotype of ADAM12 expression in ccRCC patients. MATERIALS AND METHODS: In this retrospective study, we enrolled 202 ccRCC patients divided into two groups: ccRCC patients with ADAM12 expression (n = 35) and ccRCC patients without ADAM12 expression (n = 167). Different imaging features were evaluated on CT scan at first diagnosis. The statistical significance threshold was set at p < 0.05. RESULTS: A statistically significant correlation was found with larger primary tumor size (p = 0.020), ill-defined tumor margins (p = 0.044), tumor necrosis (p = 0.011), and collecting system invasion (p = 0.014). CONCLUSION: This study demonstrates CT imaging features associated to ADAM12 expression in ccRCC. These results could help delve into ADAM12 gene status through CT approach and to further investigate towards the development of targeted therapies in ccRCC.

Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity.

Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.