MR-guided focused ultrasound-induced blood-brain barrier opening for brain metastasis: a review.

Although the therapeutic armamentarium for brain metastases (BMs) has been expanded from innovative surgical techniques and radiotherapy to include targeted therapies and immunotherapy, the prognosis of BMs remains poor. Despite the proven efficacy of numerous compounds in preclinical studies, the limited penetration of promising therapeutic agents across the blood-brain barrier (BBB) remains an unaddressed issue. Recently, low-intensity magnetic resonance-guided focused ultrasound (MRgFUS) in combination with microbubbles has been shown to overcome vascular and cellular transport barriers in the brain and tumor microenvironment, resulting in increased drug diffusion and preliminary effective results. Preclinical studies have investigated the increased penetration of many therapeutic agents including doxorubicin, trastuzumab, and ipilimumab into the CNS with promising results. Furthermore, anticancer drugs combined with MRgFUS-induced BBB opening have been demonstrated to improve animal survival and slow tumor progression. Accordingly, the first clinical trial has recently been launched and hopefully the results will provide evidence for the safety and efficacy of drug delivery enhanced by MRgFUS-induced BBB opening in BMs. This review aims to provide an overview of transcranial low-intensity MRgFUS application for BBB disruption and a comprehensive overview of the most relevant evidence in the treatment of BMs.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

INTRODUCTION: The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. PATIENTS AND METHODS: Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. RESULTS: Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). CONCLUSIONS: Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

Conventional MRI-Derived Biomarkers of Adult-Type Diffuse Glioma Molecular Subtypes: A Comprehensive Review.

The introduction of molecular criteria into the classification of diffuse gliomas has added interesting practical implications to glioma management. This has created a new clinical need for correlating imaging characteristics with glioma genotypes, also known as radiogenomics or imaging genomics. Although many studies have primarily focused on the use of advanced magnetic resonance imaging (MRI) techniques for radiogenomics purposes, conventional MRI sequences remain the reference point in the study and characterization of brain tumors. A summary of the conventional imaging features of glioma molecular subtypes should be useful as a tool for daily diagnostic brain tumor management. Hence, this article aims to summarize the conventional MRI features of glioma molecular subtypes in light of the recent literature.

Structural and functional brain networks of individual differences in trait anger and anger control: An unsupervised machine learning study.

The ability to experience, use and eventually control anger is crucial to maintain well-being and build healthy relationships. Despite its relevance, the neural mechanisms behind individual differences in experiencing and controlling anger are poorly understood. To elucidate these points, we employed an unsupervised machine learning approach based on independent component analysis to test the hypothesis that specific functional and structural networks are associated with individual differences in trait anger and anger control. Structural and functional resting state images of 71 subjects as well as their scores from the State-Trait Anger Expression Inventory entered the analyses. At a structural level, the concentration of grey matter in a network including ventromedial temporal areas, posterior cingulate, fusiform gyrus and cerebellum was associated with trait anger. The higher the concentration, the higher the proneness to experience anger in daily life due to the greater tendency to orient attention towards aversive events and interpret them with higher hostility. At a functional level, the activity of the default mode network (DMN) was associated with anger control. The higher the DMN temporal frequency, the stronger the exerted control over anger, thus extending previous evidence on the role of the DMN in regulating cognitive and emotional functions in the domain of anger. Taken together, these results show, for the first time, two specialized brain networks for encoding individual differences in trait anger and anger control.

Clinical and Brain Imaging Findings in a Child with Vitamin B12 Deficiency.

Vitamin B12 (Vit-B12) deficiency is a rare and treatable cause of failure to thrive and delayed development in infants who are exclusively breastfed. Apart from genetic causes, it can be related to a malabsorption syndrome or when the mother follows a strict vegetarian or vegan diet, causing a low hepatic storage of Vit-B12 in the infant at birth. As the neurological symptoms are nonspecific, a brain magnetic resonance imaging (MRI) exam is usually performed to rule out primary causes of neurodevelopmental delay. Findings related to brain atrophy are usually observed. A favorable response is achieved with Vit-B12 therapy, and neurological symptoms dramatically improve within a few days after the treatment. We present the case of an infant with severe Vit-B12 deficiency, exclusively breastfed by his young vegan mother, and whose clinical symptoms together with MRI findings improved after treatment. Brain atrophy recovery after Vit-B12 therapy has been seldom documented.

Predict Treatment Response by Magnetic Resonance Diffusion Weighted Imaging: A Preliminary Study on 46 Meningiomas Treated with Proton-Therapy.

OBJECTIVE: a considerable subgroup of meningiomas (MN) exhibit indolent and insidious growth. Strategies to detect earlier treatment responses based on tumour biology rather than on size can be useful. We aimed to characterize therapy-induced changes in the apparent diffusion coefficient (ADC) of MN treated with proton-therapy (PT), determining whether the pre- and early post-treatment ADC values may predict tumour response. METHODS: Forty-four subjects with MN treated with PT were retrospectively enrolled. All patients underwent conventional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) at baseline and each 3 months for a follow-up period up to 36 months after the beginning of PT. Mean relative ADC (rADCm) values of 46 MN were measured at each exam. The volume variation percentage (VV) for each MN was calculated. The Wilcoxon test was used to assess the differences in rADCm values between pre-treatment and post-treatment exams. Patients were grouped in terms of VV (threshold -20%). A p < 0.05 was considered statistically significant for all the tests. RESULTS: A significant progressive increase of rADCm values was detected at each time point when compared to baseline rADCm (p < 0.05). Subjects that showed higher pre-treatment rADCm values had no significant volume changes or showed volume increase, while subjects that showed a VV < -20% had significantly lower pre-treatment rADCm values. Higher and earlier rADCm increases (3 months) are related to greater volume reduction. CONCLUSION: In MN treated with PT, pre-treatment rADCm values and longitudinal rADCm changes may predict treatment response.

Imaging of Substantia Nigra in Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by motor and non-motor symptoms due to the degeneration of the pars compacta of the substantia nigra (SNc) with dopaminergic denervation of the striatum. Although the diagnosis of PD is principally based on a clinical assessment, great efforts have been expended over the past two decades to evaluate reliable biomarkers for PD. Among these biomarkers, magnetic resonance imaging (MRI)-based biomarkers may play a key role. Conventional MRI sequences are considered by many in the field to have low sensitivity, while advanced pulse sequences and ultra-high-field MRI techniques have brought many advantages, particularly regarding the study of brainstem and subcortical structures. Nowadays, nigrosome imaging, neuromelanine-sensitive sequences, iron-sensitive sequences, and advanced diffusion weighted imaging techniques afford new insights to the non-invasive study of the SNc. The use of these imaging methods, alone or in combination, may also help to discriminate PD patients from control patients, in addition to discriminating atypical parkinsonian syndromes (PS). A total of 92 articles were identified from an extensive review of the literature on PubMed in order to ascertain the-state-of-the-art of MRI techniques, as applied to the study of SNc in PD patients, as well as their potential future applications as imaging biomarkers of disease. Whilst none of these MRI-imaging biomarkers could be successfully validated for routine clinical practice, in achieving high levels of accuracy and reproducibility in the diagnosis of PD, a multimodal MRI-PD protocol may assist neuroradiologists and clinicians in the early and differential diagnosis of a wide spectrum of neurodegenerative disorders.

Imaging of inner ear malformations: a primer for radiologists.

In the multidisciplinary management of patients with inner ear malformations (IEMs), the correct diagnosis makes the differences in terms of clinical and surgical treatment. The complex anatomical landscape of the inner ear, comprising several small structures, makes imaging of this region particularly challenging for general radiologists. Imaging techniques are important for identifying the presence and defining the type of IEM and the cochlear nerve condition. High-resolution magnetic resonance imaging (MRI) sequences and high-resolution computed tomography (HRCT) are the mainstay imaging techniques in this area. Dedicated MRI and HRCT protocols play an important role in the diagnosis and treatment of patients with inner ear disease. The most suitable technique should be selected depending on the clinical setting. However, in cases of congenital malformation of the inner ear, these techniques should be considered complementary. Since prompt intervention has a positive impact on the treatment outcomes, early diagnosis of IEMs is very important in the management of deaf patients. This article reviews the key concepts of IEMs for clinical radiologists by focusing on recent literature updates, discusses the principal imaging findings and clinical implications for every IEM subgroup, thus providing a practical diagnostic approach.

Brain Mapping-Aided SupraTotal Resection (SpTR) of Brain Tumors: The Role of Brain Connectivity.

Brain gliomas require a deep knowledge of their effects on brain connectivity. Understanding the complex relationship between tumor and functional brain is the preliminary and fundamental step for the subsequent surgery. The extent of resection (EOR) is an independent variable of surgical effectiveness and it correlates with the overall survival. Until now, great efforts have been made to achieve gross total resection (GTR) as the standard of care of brain tumor patients. However, high and low-grade gliomas have an infiltrative behavior and peritumoral white matter is often infiltrated by tumoral cells. According to these evidences, many efforts have been made to push the boundary of the resection beyond the contrast-enhanced lesion core on T1w MRI, in the so called supratotal resection (SpTR). SpTR is aimed to maximize the extent of resection and thus the overall survival. SpTR of primary brain tumors is a feasible technique and its safety is improved by intraoperative neuromonitoring and advanced neuroimaging. Only transient cognitive impairments have been reported in SpTR patients compared to GTR patients. Moreover, SpTR is related to a longer overall and progression-free survival along with preserving neuro-cognitive functions and quality of life.

Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound with a 1.5 Tesla Scanner: A Prospective Intraindividual Comparison Study of Intraoperative Imaging.

BACKGROUND: High-quality intraoperative imaging is needed for optimal monitoring of patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy. In this paper, we compare the intraoperative imaging obtained with dedicated FUS-Head coil and standard body radiofrequency coil in tcMRgFUS thalamotomy using 1.5-T MR scanner. METHODS: This prospective study included adult patients undergoing tcMRgFUS for treatment of essential tremor. Intraoperative T2-weighted FRFSE sequences were acquired after the last high-energy sonication using a dedicated two-channel FUS-Head (2ch-FUS) coil and body radiofrequency (body-RF) coil. Postoperative follow-ups were performed at 48 h using an eight-channel phased-array (8ch-HEAD) coil. Two readers independently assessed the signal-to-noise ratio (SNR) and evaluated the presence of concentric lesional zones (zone I, II and III). Intraindividual differences in SNR and lesional findings were compared using the Wilcoxon signed rank sum test and McNemar test. RESULTS: Eight patients underwent tcMRgFUS thalamotomy. Intraoperative T2-weighted FRFSE images acquired using the 2ch-FUS coil demonstrated significantly higher SNR (R1 median SNR: 10.54; R2: 9.52) compared to the body-RF coil (R1: 2.96, p < 0.001; R2: 2.99, p < 0.001). The SNR was lower compared to the 48-h follow-up (p < 0.001 for both readers). Intraoperative zone I and zone II were more commonly visualized using the 2ch-FUS coil (R1, p = 0.031 and p = 0.008, R2, p = 0.016, p = 0.008), without significant differences with 48-h follow-up (p ≥ 0.063). The inter-reader agreement was almost perfect for both SNR (ICC: 0.85) and lesional findings (k: 0.82-0.91). CONCLUSIONS: In the study population, the dedicated 2ch-FUS coil significantly improved the SNR and visualization of lesional zones on intraoperative imaging during tcMRgFUS performed with a 1.5-T MR scanner.

Usefulness of 18f-FDG PET-CT in Staging, Restaging, and Response Assessment in Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Despite clinical advances, subsets of these patients continue to suffer high morbidity and mortality rates associated with their disease. Following the European guidelines for 18F-FDG PET and PET-CT imaging in pediatric oncology, the routine use of 18F-FDG PET-CT may be useful for patients affected by rhabdomyosarcoma, in staging, in the evaluation of response to therapy, and for restaging/detection of relapse. The European Pediatric Protocols are very old, and for staging and restaging, they recommend only radionuclide bone scan. The 18F-FDG PET-CT exam is listed as an optional investigation prescribed according to local availability and local protocols in the investigations panel required at the end of the treatment. We present two cases highlighting the usefulness of 18F-FDG PET-CT in managing pediatric patients affected by rhabdomyosarcoma, providing some bibliographic references.

Hemorragic presentation of Listeria Monocytogenes rhombencephalic abscess.

Listeria monocytogenes (LM) bacterium is a cause of central nervous system (CNS) infection and the most common cause of rhombencephalitis in immunocompetent elderly.A prompt identification of this condition should be always desirable, since its clinical manifestations are often unspecific with prodromal symptoms leading to high rates of morbidity and mortality if underestimated.CNS listeriosis magnetic resonance imaging (MRI) findings are generally not specific. However, in the appropriate clinical setting, focal brainstem hyperintensity on T2-weighted pulse sequences associated with ring-enhancement pattern after i.v. contrast media injection should be suspicious of LM abscess. The diagnosis cannot exempt from anamnestic-clinical-investigation data correlation to exclude mimicking.

Cerebral abscesses imaging: A practical approach.

Brain abscesses (BAs) are focal infections of the central nervous system (CNS) that start as a localised area of weakening of the brain parenchyma (cerebritis) and develops into a collection of pus surrounded by a capsule. Pyogenic (bacterial) BAs represent the majority of all BAs; in some cases, the diagnostic and therapeutic management can be challenging. Imaging has a primary role in differentiating BAs from other lesions. Conventional magnetic resonance imaging (cMRI) is essential for the identification of the lesion, its localisation and its morphological features. However, cMRI does not allow to reliably differentiate BAs from other intracranial mass lesions such as necrotic tumours. Advanced sequences, such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and proton MR spectroscopy (1H-MRS) are very useful in the differential diagnosis from other brain lesions, such as non-pyogenic abscesses or necrotic tumours, and provide essential information on structural, vascular and metabolic characteristics allowing greater neuroradiological confidence. The aim of this pictorial review is to provide a practical approach showing the added value of more advanced MRI techniques in their diagnostic management.

Malignancy course of pituitary adenoma in MEN1 syndrome: Clinical-Neuroradiological signs.

Pituitary carcinomas (PCa) are extremely rare, indistinguishable from pituitary adenomas on histopathological grounds and have a poor prognosis. Most PCa start as PRL or ACTH secreting tumors in males, with relapsing invasive behaviour, refractoriness to medical and radiotherapy and increasing hormonal levels. The presence of distant metastases is still required for the diagnosis of PCa. The association with genetic endocrine diseases must be taken into account, since it adds further risk of evolution towards malignancy. Intradural spinal metastases have also been reported, so a complete craniospinal MR evaluation is recommended, when clinically indicated. We report a case of PCa, associated with MEN1 syndrome, with evidence of meningeal spread to the tentorium cerebelli, clival dura and spinal drop metastases mimicking spinal nerves schwannomas.

Unusual diagnostic findings in temporal lobe epilepsy: A combined MRI and 18F-dopa case study.

Temporal lobe epilepsy is the most common focal epilepsy in adults and often causes pharmacoresistant seizures. Magnetic resonance imaging (MRI) and PET studies have widely demonstrated a number of morphological and molecular abnormalities in epilepsy. However, considering the dopaminergic system, only a bilateral 18F-DOPA uptake reduction within the basal ganglia has been described. We report the unusual finding of increased 18F-DOPA uptake in a patient with focal recurrent seizures and "deja vu" experiences in the setting of cortical swelling detected at MRI exam. The final diagnosis was in in keeping with hippocampal sclerosis, confirmed during follow-up MR exams. In this case 18F-DOPA uptake may represent increased dopamine transport induced by seizures. Nuclear medicine physicians and radiologists should be aware of clinical and electroencephalographic findings when interpreting brain areas of tracer uptake, which are not always related to malignancy.

Biomarkers of pituitary macroadenomas aggressive behaviour: a conventional MRI and DWI 3T study.

OBJECTIVE: Pituitary macroadenomas (PAs) are usually defined as benign intracranial tumors. However, they may present local aggressive course. High Ki67 labelling index (LI) values have been related to an aggressive tumor behavior. A recent clinicopathological classification of PA based on local invasiveness and proliferation indexes, divided them in groups with different prognosis. We evaluated the utility of conventional MRI (cMRI) and diffusion-weighted imaging (DWI), in predicting the Ki67- LI according the clinicopathological classification. METHODS: 17 patients (12 M and 5 F) who underwent surgical removal of a PA were studied. cMRI features, quantification of T1W and T2W signal intensity, degree of contrast uptake (enhancement ratio, ER) and apparent diffusion coefficient (ADC) values were evaluated by using a 3 T scan. Statistics included Mann-Whitney test, Spearman's test, and receiver operating characteristic analysis. A value of p ≤ 0.05 was considered significant for all the tests. RESULTS: Negative correlations were observed between Ki-67 LI, ADCm (ρ = - 0.67, p value = 0.005) and ER values (ρ = -0.62; p = 0.008). ER values were significantly lower in the proliferative PA group (p = 0.028; p = 0.017). ADCm showed sensitivity and specificity of 90 and 85% respectively into predict Ki67-LI value. A value of ADCm ≤0, 711 x 10-6 mm2 emerged as a cut-off of a value of Ki67-LI ≥ 3%. CONCLUSION: Adding quantitative measures of ADC values to cMRI could be used routinely as a non-invasive marker of specific predictive biomarker of the proliferative activity of PA. ADVANCES IN KNOWLEDGE: Routinely use of DWI on diagnostic work-up of pituitary adenomas may help in establish the likely biological aggressive lesions.

Oropharyngeal Hairy Polyp: A Case of Respiratory Failure in a Newborn.

Hairy polyps, also known as dermoid polyps (DPs), are rare benign cystic lesions of bigerminal origin that may occur in several head and neck regions, including the oropharynx. Despite their benign histopathological nature, DPs may be life threatening, due to their upper airway location, and DPs represent one of the most unusual causes of respiratory distress during the neonatal period. In this paper, we describe a case of respiratory failure in a newborn with an oropharyngeal mass that was accidentally found during difficult intubation. Magnetic resonance imaging (MRI) detected a well-defined soft tissue pedunculated mass, arising from the left oropharynx wall, consistent with an oropharyngeal DP. The newborn had a prompt recovery after trans-oral mass removal. Our case underlines the importance of imaging in differential diagnosis of children's respiratory distress, secondary to a variety of lesions within the region of the skull base or oropharynx. It allowed us to assess the origin of the lesion, as well as its relationship with the adjacent soft tissues, and to exclude intracranial extension, thus providing essential information for the surgical planning.