Mapping tissue microstructure across the human brain on a clinical scanner with soma and neurite density image metrics

Soma and neurite density image (SANDI) is an advanced diffusion magnetic resonance imaging biophysical signal model devised to probe in vivo microstructural information in the gray matter (GM). This model requires acquisitions that include b values that are at least six times higher than those used in clinical practice. Such high b values are required to disentangle the signal contribution of water diffusing in soma from that diffusing in neurites and extracellular space, while keeping the diffusion time as short as possible to minimize potential bias due to water exchange. These requirements have limited the use of SANDI only to preclinical or cutting‐edge human scanners. Here, we investigate the potential impact of neglecting water exchange in the SANDI model and present a 10‐min acquisition protocol that enables to characterize both GM and white matter (WM) on 3 T scanners. We implemented analytical simulations to (i) evaluate the stability of the fitting of SANDI parameters when diminishing the number of shells; (ii) estimate the bias due to potential exchange between neurites and extracellular space in such reduced acquisition scheme, comparing it with the bias due to experimental noise. Then, we demonstrated the feasibility and assessed the repeatability and reproducibility of our approach by computing microstructural metrics of SANDI with AMICO toolbox and other state‐of‐the‐art models on five healthy subjects. Finally, we applied our protocol to five multiple sclerosis patients. Results suggest that SANDI is a practical method to characterize WM and GM tissues in vivo on performant clinical scanners

Tucatinib's Journey from Clinical Development to Clinical Practice: New Horizons for HER2-Positive Metastatic Disease and Promising Prospects for Brain Metastatic Spread

: Approximately 20% of breast cancers (BCs) overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein with tyrosine kinase activity, encoded by ERBB2 gene. Historically, HER2 overexpression has been linked with increased disease recurrence and a worse prognosis. However, the increasing availability of different anti-HER2 compounds and combinations is progressively improving HER2-positive BC outcome, thus requiring expertise to prioritize both overall survival (OS) prolongation and quality of life, without neglecting the accessibility to further treatment lines with a low attrition rate. In this context, tucatinib, an oral tyrosine kinase inhibitor, has recently been granted approval by regulatory agencies based on evidence from the HER2CLIMB, a clinical trial which randomized patients with metastatic BC to receive trastuzumab and capecitabine with either tucatinib or placebo. A distinctive feature of this study was the inclusion of patients with new or active brain metastases (BMs) at study entry, a population traditionally excluded from clinical trials. Thus, HER2CLIMB provides the first solid evidence of an OS benefit in patients with BC and BMs, addressing a long standing unmet medical need, especially given the high incidence of central nervous system metastatic spread in patients with HER2-positive disease. This review provides an overview of the molecular and clinical landscape of tucatinib for the treatment of advanced BC. It focuses on the technological journey that drove the development of this therapeutic innovation, from preclinical data to clinical practice

Vein of Galen aneurysmal malformation in newborns: a retrospective study to describe a paradigm of treatment and identify risk factors of adverse outcome in a referral center

BackgroundVein of Galen aneurysmal malformation (VGAM) is a rare cerebral vascular malformation associated with significant morbidity and mortality. Newborns with VGAM without adequate treatment may develop rapidly deteriorating high output heart failure (HOHF) and are at risk for severe neurological outcomes.ObjectiveTo describe the clinical course and management of newborns with VGAM, and identify which echocardiographic and neuroradiologic factors may be associated with severe heart failure at birth and adverse short term outcomes.MethodsThis is a single center retrospective cohort study including all consecutive newborns with VGAM admitted to Gaslini Children's Hospital between 2009 and 2022. We reviewed clinical data, intensive care support, fetal and neonatal cardiologic and neuroradiologic findings and we studied the association with severe HOHF, endovascular complications and death.ResultsOut of 40 newborns, 17 (42.5%) developed severe HOHF requiring early endovascular procedures. Medical treatment was focused on the main components of HOHF by providing inotropic support and peripheral vasodilation. Pulmonary vasodilators were avoided to reduce the negative effects of pulmonary overflow and prevent vascular remodeling. Reduction of the obligatory left to right shunt through the VGAM was possible only through endovascular treatment. Fetal cardiothoracic ratio was significantly associated with severe HOHF at birth and death. Cardiologic parameters of right ventricular overload, pulmonary hypertension and systemic steal were the leading findings associated with haemodynamic compromise at birth. The mediolateral diameter of the straight or falcine sinus at its shortest section (SS-MD), and arterial pseudofeeders were significantly associated with severe HOHF at birth in prenatal and postnatal assessments. None of the postnatal echocardiographic and MRI variables, nor a higher inotropic support were associated with major periprocedural complications or death. Mortality was due to palliation for congenital severe brain damage (4/40, 10%), or major periprocedural complications (3/40, 7.5%). None of the patients died due to HOHF and multiorgan failure. Overall survival at discharge was 82.5% (33/40).ConclusionsThe complexity of neonatal VGAM pathophysiology requires a multidisciplinary approach, specialized intensive care management, and early endovascular treatment to reduce mortality and optimize clinical outcomes. Cardiologic and neuroradiologic parameters are key to define risk stratification and treatment strategies

Dynamic Contrast-Enhanced MRI in the Study of Brain Tumors. Comparison Between the Extended Tofts-Kety Model and a Phenomenological Universalities (PUN) Algorithm

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a well-established technique for studying blood\ue2\u80\u93brain barrier (BBB) permeability that allows measurements to be made for a wide range of brain pathologies, including multiple sclerosis and brain tumors (BT). This latter application is particularly interesting, because high-grade gliomas are characterized by increased microvascular permeability and a loss of BBB function due to the structural abnormalities of the endothelial layer. In this study, we compared the extended Tofts-Kety (ETK) model and an extended derivate class from phenomenological universalities called EU1 in 30 adult patients with different BT grades. A total of 75 regions of interest were manually drawn on the MRI and subsequently analyzed using the ETK and EU1 algorithms. Significant linear correlations were found among the parameters obtained by these two algorithms. The means of R2 obtained using ETK and EU1 models for high-grade tumors were 0.81 and 0.91, while those for low-grade tumors were 0.82 and 0.85, respectively; therefore, these two models are equivalent. In conclusion, we can confirm that the application of the EU1 model to the DCE-MRI experimental data might be a useful alternative to pharmacokinetic models in the study of BT, because the analytic results can be generated more quickly and easily than with the ETK model

A fatal and unusual iatrogenic fourth right lumbar artery injury complicating wrong-level hemilaminectomy: a case report and literature review

The authors describe an unusual case of a fatal iatrogenic fourth lumbar artery injury during left hemilaminectomy in a 38-year-old woman. At autopsy, gross inspection revealed hemoperitoneum with 1,800\ue2\u80\u89ml of free blood and massive retroperitoneal extravasation. A laceration with irregular and jagged margins was detected on the wall of the fourth right lumbar artery. The autopsy and the post-mortem TC investigations demonstrated that wrong-level hemilaminectomy was performed for the herniated disc