Truncating variants in the penultimate exon of TGFBR1 escaping nonsense-mediated mRNA decay cause Loeys-Dietz syndrome.

Pathogenic variants in TGFBR1 are a common cause of Loeys-Dietz syndrome (LDS) characterized by life-threatening aortic and arterial disease. Generally, these are missense changes in highly conserved amino acids in the serine-threonine kinase domain. Conversely, nonsense, frameshift, or specific missense changes in the ligand-binding extracellular domain cause multiple self-healing squamous epithelioma (MSSE) lacking the cardiovascular phenotype. Here, we report on two novel variants in the penultimate exon 8 of TGFBR1 were identified in 3 patients from two unrelated LDS families: both were predicted to cause frameshift and premature stop codons (Gln448Profs*15 and Cys446Asnfs*4) resulting in truncated TGFBR1 proteins lacking the last 43 and 56 amino acid residues, respectively. These were classified as variants of uncertain significance based on current criteria. Transcript expression analyses revealed both mutant alleles escaped nonsense-mediated mRNA decay. Functional characterization in patient's dermal fibroblasts showed paradoxically enhanced TGFß signaling, as observed for pathogenic missense TGFBR1 changes causative of LDS. In summary, we expanded the allelic repertoire of LDS-associated TGFBR1 variants to include truncating variants escaping nonsense-mediated mRNA decay. Our data highlight the importance of functional studies in variants interpretation for correct clinical diagnosis.

Diffusion kurtosis imaging and standard diffusion imaging in the magnetic resonance imaging assessment of prostate cancer.

Background and Objective: In recent years, magnetic resonance imaging (MRI) has shown excellent results in the study of the prostate gland. MRI has indeed shown to be advantageous in the prostate cancer (PCa) detection, as in guiding targeting biopsy, improving its diagnostic yield. Although current acquisition protocols provide for multiparametric acquisition, recent evidence has shown that biparametric protocols can be non-inferior in PCa detection. Diffusion-weighted imaging (DWI) sequence, in particular, plays a key role, particularly in the peripheral zone which accounts for the larger part of the prostate. High b-values are generally recommended, although with the possibility of obtaining non-Gaussian diffusion effects, which requires a more sophisticated model for the analysis, namely through the diffusion kurtosis imaging (DKI). Purpose of this narrative review was to analyze the current applications and clinical evidence regarding the use of DKI with a main focus on PCa detection, also in comparison with DWI. Methods: This narrative review synthesized the findings of literature retrieved from main researches, narrative and systematic reviews, and meta-analyses obtained from PubMed. Key Content and Findings: DKI analyses the non-Gaussian water diffusivity and describe the effect of signal intensity decay related to high b-value through two main metrics (Dapp and Kapp). Differently from DWI-apparent diffusion coefficient (DWI-ADC) which reflects only water restriction outside of cells, DKI metrics are supposed to represent also the direct interaction of water molecules with cell membranes and intracellular compounds. This review describes current evidence on ADC and DKI metrics in clinical imaging, and finally collect the results derived from the main articles focused on DWI and DKI models in detecting PCa. Conclusions: DKI advantages, compared to conventional ADC analysis, still remain controversial. Wider application and greater technical knowledge of DKI, however, may help in proving its intrinsic validity in the field of oncology and therefore in the study of clinically significant PCa. Finally, a deep understanding of DKI is important for radiologists to better understand what Kapp and Dapp mean in the context of different cancer and how these metrics may vary specifically in PCa imaging.

Stress Perfusion Cardiac Magnetic Resonance in Long-Standing Non-Infarcted Chronic Coronary Syndrome with Preserved Systolic Function.

(1) Background: The impact of imaging-derived ischemia is still under debate and the role of stress perfusion cardiac magnetic resonance (spCMR) in non-high-risk patient still needs to be clarified. The aim of this study was to evaluate the impact of spCMR in a case series of stable long-standing chronic coronary syndrome (CCS) patients with ischemia and no other risk factor. (2) Methods: This is a historical prospective study including 35 patients with history of long-standing CCS who underwent coronary CT angiography (CCTA) and additional adenosine spCMR. Clinical and imaging findings were included in the analysis. Primary outcomes were HF (heart failure) and all major cardiac events (MACE) including death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, or resuscitated cardiac arrest. (3) Results: Mean follow-up was 3.7 years (IQR: from 1 to 6). Mean ejection fraction was 61 ± 8%. Twelve patients (31%) referred primary outcomes. Probability of experiencing primary outcomes based on symptoms was 62% and increased to 67% and 91% when multivessel disease and ischemia, respectively, were considered. Higher ischemic burden was predictive of disease progression (OR: 1.59, 95%CI: 1.18-2.14; p-value = 0.002). spCMR model resulted non inferior to the model comprising all variables (4) Conclusions: In vivo spCMR-modeling including perfusion and strain anomalies could represent a powerful tool in long-standing CCS, even when conventional imaging predictors are missing.

Advanced Magnetic Resonance Imaging (MRI) Techniques: Technical Principles and Applications in Nanomedicine.

In the last decades, nanotechnology has been used in a wide range of biomedical applications, both diagnostic and therapeutic. In this scenario, imaging techniques represent a fundamental tool to obtain information about the properties of nanoconstructs and their interactions with the biological environment in preclinical and clinical settings. This paper reviews the state of the art of the application of magnetic resonance imaging in the field of nanomedicine, as well as the use of nanoparticles as diagnostic and therapeutic tools, especially in cancer, including the characteristics that hinder the use of nanoparticles in clinical practice.

Basics in Magnetic Resonance guided Focused Ultrasound: technical basis and clinical application. A brief overview.

First applications of high focused ultrasound as intracranial ablative therapy were firstly described in early 50'. Since then, the technological innovations have shown an increasingly safe and effective face of this technique. And in the last few years, Magnetic Resonance (MR) guided Focused Ultrasound (gFUS) has become a valid minimally invasive technique in the treatment of several diseases, from bone tumors to symptomatic uterine fibroids or essential tremors. MR guidance, through the tomographic view, offers the advantage of an accurate target detection and treatment planning. Moreover, real-time monitoring sequences allow to avoid non-target ablation. An adequate knowledge of FUS is essential to understand its clinical effectiveness. Therefore, this brief review aims to debate the physical characteristics of US and the main fields of clinical application.

Intracranial ependymomas: The role of advanced neuroimaging in diagnosis and management.

Intracranial ependymomas represent a rare subgroup of glial tumours, showing a wide variety of imaging characteristics, often representing a challenging diagnosis for neuroradiologists. Here, we review the most recent scientific Literature on intracranial ependymomas, highlighting the most characteristic computed tomography and magnetic resonance imaging features of these neoplasms, along with epidemiologic data, recent classification aspects, clinical presentation and conventional therapeutic strategies. In addition, we report an illustrative case of an 18-year-old girl presenting with an intracranial supratentorial, anaplastic ependymoma, with the aim of contributing to the existing knowledge and comprehension of this rare tumour.

Appropriate use criteria for cardiovascular magnetic resonance imaging (CMR): SIC-SIRM position paper part 1 (ischemic and congenital heart diseases, cardio-oncology, cardiac masses and heart transplant).

Cardiac magnetic resonance (CMR) has emerged as new mainstream technique for the evaluation of patients with cardiac diseases, providing unique information to support clinical decision-making. This document has been developed by a joined group of experts of the Italian Society of Cardiology and Italian society of Radiology and aims to produce an updated consensus statement about the current state of technology and clinical applications of CMR. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac radiology. Part 1 of the document will cover ischemic heart disease, congenital heart disease, cardio-oncology, cardiac masses and heart transplant.

A case of segmental hepatic necrosis complicating oxaliplatin and capecitabine chemotherapy A case report and review of the literature.

Chemotherapy is associated with different patterns of histopathological changes of the non-tumor-bearing liver. Hepatic infarction represents a relatively rare condition; the prevalence in several series of consecutive autopsies is 1.1%. To the best of our knowledge, no cases of liver infarction secondary to chemotherapy have been reported to date. We report a case of segmental hepatic infarction following the adjuvant chemotherapy with Oxaliplatin and Capecitabine in a patient who had undergone total gastrectomy and distal esophagectomy for gastric cancer. Liver infarction is usually managed by conservative therapy; interventional procedures such as percutaneous imaging-guided drainage or surgical evacuation should be reserved in cases where septic complications occur, with development of a hepatic abscess from the necrotic area. It is important to avoid misdiagnoses with liver metastases in order to define the most appropriate clinical management strategy. KEY WORDS: Adjuvant chemotherapy, Gastric cancer, Liver infarction, Hepatic necrosis.

Masses in right side of the heart: spectrum of imaging findings.

Primary heart tumors are rare, benign tumors represent the majority of these. If a cardiac mass is found, the probability that it is a metastasis or a so-called "pseudo-mass" is extremely higher than a primary tumor. The detection of a heart mass during a transthoracic echocardiography (TE) is often unexpected. The TE assessment can be difficult, particularly if the mass is located at the level of the right chambers. Cardiac Computed Tomography (CCT) can be useful in anatomical evaluation and Cardiac Magnetic Resonance (CMR) for masses characterization as well. We provide an overview of right cardiac masses and their imaging futures.

Diagnostic and interventional management of infective spine diseases.

Spondylodiscitis (SD) is one of the main causes of back pain. Although the low mortality, high morbidity is related to spondilodiscitys, leading spine instability, chronic pain or neurological deficit. Diagnostic imaging plays a primary role in diagnosing spondylodiscitis. However different accuracy is highlighted by different diagnostic tool, depending also on timing of disease which represents a cardinal element for the phenotypic manifestation of the disease, beyond spatial resolution and tissue characterization proper of specific modality imaging. Conventional Radiology (CR), Computed Tomography (CT) and MRI (Magnetic Resonance Imaging) all have proven to be of primary importance in the approach to spondylodiscitis, although magnetic resonance imaging has demonstrated the greatest advantage in identifying the disease from its earliest stages, demonstrating high sensitivity and specificity (92% and 96%, respectively). This review focus on the role of different imaging modality in the approach to the spondylodiscitis, also addressing the role of interventional radiology that is pivotal not only for a diagnosis of certainty through biopsy, but also for a minimally-invasive treatment of paravertebral abscesses spondylodiscitis-related.

The sub-millisievert era in CTCA: the technical basis of the new radiation dose approach.

Computed tomography coronary angiography (CTCA) has become a cornerstone in the diagnostic process of the heart disease. Although the cardiac imaging with interventional procedures is responsible for approximately 40% of the cumulative effective dose in medical imaging, a relevant radiation dose reduction over the last decade was obtained, with the beginning of the sub-mSv era in CTCA. The main technical basis to obtain a radiation dose reduction in CTCA is the use of a low tube voltage, the adoption of a prospective electrocardiogram-triggering spiral protocol and the application of the tube current modulation with the iterative reconstruction technique. Nevertheless, CTCA examinations are characterized by a wide range of radiation doses between different radiology departments. Moreover, the dose exposure in CTCA is extremely important because the benefit-risk calculus in comparison with other modalities also depends on it. Finally, because anatomical evaluation not adequately predicts the hemodynamic relevance of coronary stenosis, a low radiation dose in routine CTCA would allow the greatest use of the myocardial CT perfusion, fractional flow reserve-CT, dual-energy CT and artificial intelligence, to shift focus from morphological assessment to a comprehensive morphological and functional evaluation of the stenosis. Therefore, the aim of this work is to summarize the correct use of the technical basis in order that CTCA becomes an established examination for assessment of the coronary artery disease with low radiation dose.

In vivo radiation dosimetry and image quality of turbo-flash and retrospective dual-source CT coronary angiography.

PURPOSE: To compare measured radiation dose (MD), estimated radiation dose (ED) and image quality in coronary computed tomography between turbo-flash (TFP) and retrospective protocol (RP) and correlate MD with size-specific dose estimates (SSDE). MATERIALS AND METHODS: In this prospective study, we selected 68 patients (mean age, 59.2 ± 9.7 years) undergoing 192 × 2 dual-source CT (SOMATOM Force, Siemens) to rule out coronary artery disease. Thirty-one underwent TFP and 37 RP. To evaluate in vivo MD, thermoluminescent dosimeters were placed, superficially, at thyroid and heart level, left breast areola and left hemi-thorax. MD in each site, and ED parameters, such as volume CT dose index (CTDIvol), SSDE, dose length product (DLP), effective dose (E), were compared between two protocols with a t test. Image quality was compared between two protocols. Inter-observer agreement was evaluated with a kappa coefficient (k). In each protocol, MD was correlated with SSDE using a Pearson coefficient (r). RESULTS: Comparing TFP and RP, MD at thyroid (1.43 vs. 2.58 mGy; p = 0.0408), heart (3.58 vs. 28.72 mGy; p < 0.0001), left breast areola (3.00 vs. 24.21 mGy; p < 0.0001) and left hemi-thorax (2.68 vs. 24.03 mGy; p < 0.0001), CTDIvol, SSDE, DLP and E were significantly lower. Differences in image quality were not statistically significant. Inter-observer agreement was good (k = 0.796) in TFP and very good (k = 0.817) in RP. MD and SSDE excellently correlated with TFP (r = 0.9298, p < 0.0001) and RP (r = 0.9753, p < 0.0001). CONCLUSIONS: With TFP, MD, CTDIvol, SSDE, DLP and E were significantly lower, than with RP. Image quality was similar between two protocols. MD correlated excellently with SSDE in each protocol.

Apparent diffusion coefficient magnetic resonance imaging (ADC-MRI) in the axillary breast cancer lymph node metastasis detection: a narrative review.

The presence of axillary lymph nodes metastases in breast cancer is the most significant prognostic factor, with a great impact on morbidity, disease-related survival and management of oncological therapies; for this reason, adequate imaging evaluation is strictly necessary. Physical examination is not enough sensitive to assess breast cancer nodal status; axillary ultrasonography (US) is commonly used to detect suspected or occult nodal metastasis, providing exclusively morphological evaluation, with low sensitivity and positive predictive value. Currently, sentinel lymph node biopsy (SLNB) and/or axillary dissection are the milestone for the diagnostic assessment of axillary lymph node metastases, although its related morbidity. The impact of magnetic resonance imaging (MRI) in the detection of nodal metastases has been widely investigated, as it continues to represent the most promising imaging modality in the breast cancer management. In particular, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values represent additional reliable non-contrast sequences, able to improve the diagnostic accuracy of breast cancer MRI evaluation. Several studies largely demonstrated the usefulness of implementing DWI/ADC MRI in the characterization of breast lesions. Herein, in the light of our clinical experience, we perform a review of the literature regarding the diagnostic performance and accuracy of ADC value as potential pre-operative tool to define metastatic involvement of nodal structures in breast cancer patients. For the purpose of this review, PubMed, Web of Science, and SCOPUS electronic databases were searched with different combinations of "axillary lymph node", "breast cancer", "MRI/ADC", "breast MRI" keywords. All original articles, reviews and metanalyses were included.

Biparametric (bp) and multiparametric (mp) magnetic resonance imaging (MRI) approach to prostate cancer disease: a narrative review of current debate on dynamic contrast enhancement.

Prostate cancer is the most common malignancy in male population. Over the last few years, magnetic resonance imaging (MRI) has proved to be a robust clinical tool for identification and staging of clinically significant prostate cancer. Though suggestions by the European Society of Urogenital Radiology to use complete multiparametric (mp) T2-weighted/diffusion weighted imaging (DWI)/dynamic contrast enhancement (DCE) acquisition for all prostate MRI examinations, the real advantage of functional DCE remains a matter of debate. Recent studies demonstrate that biparametric (bp) and mp approaches have similar accuracy, but controversial evidences remain, and the specific potential benefits of contrast medium administration are still poorly discussed in literature. The bp approach is in fact sufficient in most cases to adequately identify a negative test, or to accurately define the degree of aggressiveness of a lesion, especially if larger or with major characteristics of malignancy. This feature would give the DCE a secondary role, probably limited to a second evaluation of the lesion location, for detecting small cancer or in case of controversy. However, DCE has proved to increase the sensitivity of prostate MRI, though a less specificity. Therefore, an appropriate decision algorithm is needed to standardize the MRI approach. Aim of this review study was to provide a schematic description of bpMRI and mpMRI approaches in the study of prostatic anatomy, focusing on comparative validity and current DCE application. Additional theoretical considerations on prostate MRI are provided.

Magnetic resonance severity index assessed by T1-weighted imaging for acute pancreatitis: correlation with clinical outcomes and grading of the revised Atlanta classification-a narrative review.

Acute pancreatitis (AP) is a common disease that may involve pancreas and peripancreatic tissues with a prevalence of up to 50 per 100,000 individuals for year. The Atlanta classification was assessed for the first time in 1992 and modified in 2012 in order to describe morphological features of AP and its complications. AP can be morphologically distinguished in two main types: interstitial edematous pancreatitis (IEP) and necrotizing pancreatitis (NEP). This classification is very important because the presence of necrosis is directly linked to local or systemic complications, hospital stays and death. Magnetic resonance (MR) is very useful to characterize morphological features in AP and its abdominal complications. Particularly we would like to underline the diagnostic, staging and prognostic role of T1-weighted images with fat suppression that could be significant to assess many features of the AP inflammatory process and its complications (detection of the pancreatic contour, pancreatic necrosis, presence of haemorrhage). Signs of inflammatory and edema are instead observed by T1-weighted images. MR cholangiopancreatography (MRCP) is necessary to study the main pancreatic duct and the extrahepatic biliary tract and contrast-enhancement magnetic resonance imaging (MRI) allows to assess the extent of necrosis and vascular injuries.

Correlation between ADC values and Gleason score in evaluation of prostate cancer: multicentre experience and review of the literature.

Prostate cancer (PCa) is one of the most common cancers in male population. Multiparametric prostate magnetic resonance imaging (mp-MRI) has assumed a primary role in the diagnosis of PCa, combining morphological and functional data. Among different sequences, functional diffusion weighted imaging (DWI) is a powerful clinical tool which provides information about tissue on a cellular level. However, there is a considerable overlap between either BPH (Benign Prostate Hypertrophy) and prostatic cancer condition, as a different DWI signal intensity could be shown in the normal architecture gland. Apparent diffusion coefficient (ADC) has shown an increasing accuracy in addition to the DWI analysis in detection and localization of PCa. Notably, ADC maps derived DWI sequences has shown an overall high correlation with Gleason score (GS), considering the importance of an accurate grading of focal lesion, as main predictor factor. Furthermore, beyond the comparative analysis with DWI, ADC values has proven to be an useful marker of tumor aggressiveness, providing quantitative information on tumor characteristics according with GS and Gleason pattern, even more strenuous data are needed in order to verify which ADC analysis is more accurate.

High-resolution magnetic resonance imaging at 3T of pituitary gland: advantages and pitfalls.

Magnetic resonance imaging (MRI) is the primary imaging tool for the evaluation of pituitary gland pathology. In the last decades, MRI with high-field scanners has become widely used in clinical practice, leading to significant improvements in image quality mainly thanks to a superior spatial resolution and signal intensity. Moreover, several advanced functional MRI sequences have been implemented for pituitary imaging, providing valuable information in diagnostic and presurgical planning of pituitary adenomas. Higher field strength presents however some technical pitfalls to be aware of. The purpose of this article is to review the state of the art of high-resolution MRI of the pituitary gland at 3 Tesla (3T), with a particular focus on the main benefits and the possible limitations of higher field imaging.

Nerve root metastasis of gastric adenocarcinoma: A case report and review of the literature.

INTRODUCTION: Nerve root metastasis without extension from an adjacent process has been seldom reported in case of solid tumors. We describe a case of solitary nerve root metastasis of gastric adenocarcinoma, likely due to hematogenous spread. CASE PRESENTATION: A 75-year-old man presented with radiculopathy refractory to medical treatment. MRI and CT demonstrated a right-sided S1 nerve root mass involving the spinal ganglion in its intra-foraminal region with avid enhancement, initial erosive bone changes on sacral foramina and focal hyperaccumulation on 18F - FDG CT-PET, suspicious for metastasis. The histopathological examination confirmed a metastasis of gastric adenocarcinoma. DISCUSSION: A review of the current literature revealed only ten cases of hematogenous metastases to spinal nerve root ganglia; the primary lesions in those cases were an oat cell carcinoma of the lung, two cases of colonic adenocarcinoma, a case of uterine adenocarcinoma, a ductal breast carcinoma, a Ewing's sarcoma, a Renal Cell Carcinoma, a gastro-intestinal stromal tumor, a follicular thyroid carcinoma, a pulmonary adenocarcinoma. CONCLUSION: In the setting of a known malignancy, a nerve root metastasis should be considered in the differential diagnosis of a nerve root mass, although it occurs very rarely.

Neuroimaging in emergency: a review of possible role of pineal gland disease.

The pineal gland can be involved in a variety of neoplastic and congenital masses and tumors. Pineal gland neoplasms occur more frequently in children, accounting for 3-8% of intracranial tumors in the pediatric population. Pineal cysts are small lesions usually asymptomatic and encountered incidentally. Pathologic processes involving the pineal region produce signs and symptoms related to the mass effect on the adjacent structures and invasion of surrounding structures. These include several acute symptoms, such as increased intracranial pressure syndrome from obstruction of the aqueduct and consequent hydrocephalus, and Parinaud syndrome. Pineal apoplexy is rare and refers to the sudden neurological deterioration following hemorrhage in the pineal gland, most commonly into a pineal cyst. Knowledge of the clinical presentation and imaging features of these lesions is essential to narrow the differential diagnosis, especially when presenting with acute onset.

Magnetic resonance enterography (MRE) and ultrasonography (US) in the study of the small bowel in Crohn's disease: state of the art and review of the literature.

Crohn's disease (CD) is a chronic idiopathic disease and its diagnosis is based on a combination of clinical symptoms, laboratory tests and imaging data. There isn't a diagnostic gold standard: the ileocolonoscopy with mucosal biopsies represents the standard for luminal disease, while cross-sectional imaging such as Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) can show transmural alterations and extraintestinal manifestations. CD is usually diagnosed in the young age and after baseline diagnosis, the patients have to undergo to variable follow-up depending on remission or active disease. The aim of our review is to compare Magnetic Resonance Enterography (MRE) to Ultrasonography (US) in the follow-up of CD.