Real-word application of the AT(N) classification and disease-modifying treatment eligibility in a hospital-based cohort.

BACKGROUND AND OBJECTIVES: The AT(N) classification system stratifies patients based on biomarker profiles, including amyloid-beta deposition (A), tau pathology (T), and neurodegeneration (N). This study aims to apply the AT(N) classification to a hospital-based cohort of patients with cognitive decline and/or dementia, within and outside the Alzheimer's disease (AD) continuum, to enhance our understanding of the multidimensional aspects of AD and related disorders. Furthermore, we wish to investigate how many cases from our cohort would be eligible for the available disease modifying treatments, such as aducanemab and lecanemab. METHODS: We conducted a retrospective evaluation of 429 patients referred to the Memory Center of IRCCS San Raffaele Hospital in Milan. Patients underwent clinical/neuropsychological assessments, lumbar puncture, structural brain imaging, and positron emission tomography (FDG-PET). Patients were stratified according to AT(N) classification, group comparisons were performed and the number of eligible cases for anti-ß amyloid monoclonal antibodies was calculated. RESULTS: Sociodemographic and clinical features were similar across groups. The most represented group was A + T + N + accounting for 38% of cases, followed by A + T - N + (21%) and A - T - N + (20%). Although the clinical presentation was similar, the A + T + N + group showed more severe cognitive impairment in memory, language, attention, executive, and visuospatial functions compared to other AT(N) groups. Notably, T + patients demonstrated greater memory complaints compared to T - cases. FDG-PET outperformed MRI and CT in distinguishing A + from A - patients. Although 61% of the observed cases were A + , only 17% of them were eligible for amyloid-targeting treatments. DISCUSSION: The AT(N) classification is applicable in a real-world clinical setting. The classification system provided insights into clinical management and treatment strategies. Low cognitive performance and specific regional FDG-PET hypometabolism at diagnosis are highly suggestive for A + T + or A - T + profiles. This work provides also a realistic picture of the proportion of AD patients eligible for disease modifying treatments emphasizing the need for early detection.

Combining semi-quantitative rating and automated brain volumetry in MRI evaluation of patients with probable behavioural variant of fronto-temporal dementia: an added value for clinical practise?

PURPOSE: To evaluate the diagnostic value of combined semiquantitative and quantitative assessment of brain atrophy in the diagnostic workup of the behavioural-variant of frontotemporal dementia (bvFTD). METHODS: Three neuroradiologists defined brain atrophy grading and identified atrophy pattern suggestive of bvFTD on 3D-T1 brain MRI of 112 subjects using a semiquantitative rating scale (Kipps'). A quantitative atrophy assessment was performed using two different automated software (Quantib® ND and Icometrix®). A combined semiquantitative and quantitative assessment of brain atrophy was made to evaluate the improvement in brain atrophy grading to identify probable bvFTD patients. RESULTS: Observers' performances in the diagnosis of bvFTD were very good for Observer 1 (k value = 0.881) and 2 (k value = 0.867), substantial for Observer 3 (k value = 0.741). Semiquantitative atrophy grading of all the observers showed a moderate and a poor correlation with the volume values calculated by Icometrix® and by Quantib® ND, respectively. For the definition of neuroradiological signs presumptive of bvFTD, the use of Icometrix® software improved the diagnostic accuracy for Observer 1 resulting in an AUC of 0.974, and for Observer 3 resulting in a AUC of 0.971 (p-value < 0.001). The use of Quantib® ND software improved the diagnostic accuracy for Observer 1 resulting in an AUC of 0.974, and for Observer 3 resulting in a AUC of 0.977 (p-value < 0.001). No improvement was observed for Observer 2. CONCLUSION: Combining semiquantitative and quantitative brain imaging evaluation allows to reduce discrepancies in the neuroradiological diagnostic workup of bvFTD by different readers.

Multidisciplinary management of patients diagnosed with von Hippel-Lindau disease: A practical review of the literature for clinicians.

Objective: The aim of the current review is to summarize the available evidence to aid clinicians in the surveillance, treatment and follow-up of the different primary tumors developed by patients diagnosed with von Hippel-Lindau (VHL) syndrome. Methods: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings. Results: VHL disease is the most common rare hereditary disorder associated with clear cell renal cell carcinoma. Affected individuals inherit a germline mutation in one VHL allele, and any somatic event that disrupt the other allele can trigger mutations, chromosomal rearrangements, or epigenetic regulations leading to oncogenesis. From a clinical perspective, patients continuously develop multiple primary tumors. Conclusion: Because VHL is considered a rare disease, very limited evidence is available for diagnosis, surveillance, active treatment with local or systemic therapy and follow-up.

Cerebral hyperdensity on CT imaging (CTHD) post-reperfusion treatment in patients with acute cerebral stroke: understanding its clinical meaning.

OBJECTIVES: To investigate the clinical meaning of brain parenchymal computed-tomography hyperdensities (CTHD) in patients treated of anterior circulation acute stroke with reperfusion therapy. METHODS: Patients were retrospectively enrolled from three different hospitals. Brain CT scans were assessed at four time points: We recorded ASPECT scores of pre-treatment CTs, assessed ASPECT scores and the presence of CTHD on post-treatment CTs acquired within 24-30 h and 24-72 h, and examined a one-month CTs follow-up to determine the ischemic evolution of CTHD. We correlated the presence of CTHD with clinical and radiological data to define its predictive and prognostic factors. RESULTS: In total, 165 patients were evaluated. At post-treatment CTs acquired within 24-30 h, 68 (41%) patients showed the presence of CTHD. On post-treatment CTs acquired within 24-72 h, 43 (63%) of the CTHD showed hemorrhagic transformation. Sixty-five (95%) out of the 68 CTHD evolved in a final ischemic brain area. Multivariate statistical analysis identified puncture to recanalization time to be the only independent factors predicting the presence of CTHD (p = 0.045). The presence of CTHD at the first post-treatment CTs was an independent factor for clinical outcome determined with mRS scores at 3-month follow-up (p = 0.05). Outcomes were worse for hemorrhagic transformation at follow-up CTs compared to the ischemic evolution of the CTHD (p = 0.01). CONCLUSIONS: The presence of CTHD at CTs imaging acquired within 24-30 h after reperfusion therapy is an independent prognostic factor of a worse clinical outcome, regardless of its ASPECT score at baseline CTs and of its hemorrhagic evolution.

Multiple hypointense veins on susceptibility weighted imaging as a promising biomarker of impaired cerebral hemodynamics in chronic steno-occlusive disease: a multiparametric MRI study.

PURPOSE: Patients with steno-occlusive arterial disease may develop cerebral hypoperfusion with possible neurologic sequelae. The aim of the study is to verify the possible role of SWI, as a marker of cerebral hypoperfusion, in the identification of patient subgroups with significant chronic occlusions/stenoses at risk of critical cerebral hypoperfusion. METHODS: We retrospectively identified 37 asymptomatic patients with chronic intra-extracranial occlusion/stenosis of the anterior circulation from a prospective brain MRI register between 2016 and 2020. All patients underwent 3 Tesla MRI. The imaging protocol included the following: SWI, 3D-FLAIR, DWI sequences, and 3D-TOF MRA. SWI findings were graded for the presence of asymmetric intracranial cortical veins (grades 1 to 4). The presence of collateralization was assessed with concomitant multiphase-CTA. FLAIR was evaluated for the presence of distal hyperintense vessels (DHVs), a described marker of flow impairment, and possible collateralization. Cerebral blood flow and arterial transit artifacts (ATAs) were evaluated at pCASL in 29 patients. RESULTS: SWI showed multiple hypointense vessels (MHVs) in 22/37 patients in the cerebral hemisphere ipsilateral to vessel occlusion/stenosis. SWI-MHV grade 1 was found in 15 patients (40.5%), grade 2 in 18 patients (48.7%), and grade 3 in 3 patients (8.1%); in one patient, SWI was graded as 4 (2.7%). A significant relationship was found among MHV, DHV, collaterals, ATAs, and hypoperfused areas on pCASL and with patients' previous neurological symptoms. CONCLUSION: SWI-MVH correlates with chronic cerebral flow impairment and is related to hypoperfusion and collateralization. It may help identify a subgroup of patients benefitting from revascularization.

Diagnostic efficacy and safety of gadoteridol compared to gadobutrol and gadoteric acid in a large sample of CNS MRI studies at 1.5T.

PURPOSE: To evaluate safety and diagnostic accuracy of gadoteridol vs. other macrocyclic gadolinium-based contrast agents (GBCAs) in a large cohort of consecutive and non-selected patients referred for CE-MRI of the CNS. MATERIAL AND METHODS: Between November 2017 and March 2018, we prospectively enrolled a consecutive cohort of patients referred for neuroradiological CE-MRI (1.5T MRI). Image quality and adverse events were assessed. Diagnostic performance was determined for a subgroup of patients with truth standard findings available. Comparison was made between patients receiving gadoteridol and patients receiving other macrocyclic GBCAs. Inter-reader agreement (kappa) between two expert neuroradiologists was calculated for the diagnosis of malignancy. RESULTS: Overall, 460 patients (220M/240F; mean age 54±16 years) were enrolled of which 230 received gadoteridol (Group 1) and 230 either gadoteric acid or gadobutrol [n=83 (36.1%) and n=147 (63.9%), respectively; Group 2]. Image quality was rated as good or excellent in both groups. The sensitivity, specificity and diagnostic accuracy for determination of malignancy was 88.2%, 96.5% and 95.4%, respectively, for Group 1 and 93.7%, 97.4% and 96.9%, respectively, for Group 2, with no significant differences between groups (P>0.75) for any determination. Inter-reader agreement for the identification of malignancy was excellent [K=0.877 (95%CI: 0.758-0.995) and K=0.818 (95%CI: 0.663-0.972) for groups 1 and 2, respectively; P=0.0913]. Adverse events occurred in 5 of 460 (1.09%) patients overall, with no significant difference (P=0.972) between groups. CONCLUSION: Gadoteridol was safe and guaranteed good image quality without significant differences when compared to gadobutrol and gadoteric acid in a wide range of CNS pathologies.

The role of CE-MRA of the supraortic vessels in the detection of associated intracranial pathology.

BACKGROUND: Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a very popular imaging technique in the evaluation of the extracranial vessels pathology, while it is not commonly used to rule out intracranial vascular pathology. On the contrary, 3D time of flight MRA (TOF-MRA) has a solid role in the study of intracranial arterial vessels disease. MATERIALS AND METHODS: One hundred and eight patients were consecutively included in the study. All patients were submitted to a 3 Tesla 3D CE-MRA imaging to rule out extracranial vessels pathology. A comparison was made with a 3D-TOF sequence acquired at the same time in the assessment of intracranial vessels diseases such as steno-occlusion, dissection, and aneurysms. RESULTS: With regard to steno-occlusive disease, Spearman's rank correlation coefficient was of 0.56 for stenosis detection and of 0.57 for occlusive disease detection. The two techniques shared similar results in the evaluation of anterior circulation, while 3D-TOF found higher grades of stenosis for posterior circulation. With regard to dissection, Spearman's rank correlation coefficient was of 0.7. 3D-TOF depicted more intramural hematoma (Spearman's rank = 0.46), while CE-MRA showed more pseudo-aneurysms (Spearman's rank = 0.56). Both the technique equally evaluated the presence of intracranial aneurysms (Spearman's rank = 1). CONCLUSION: CE-MRA can be considered a reliable tool to rule out intracranial pathology associated to supraortic steno-occlusive disease, also allowing time reduction. In the suspicion of dissection a T1-weighted sequence has to be added to detect the presence of a subacute vessel wall hematoma.

Toward a marker of upper motor neuron impairment in amyotrophic lateral sclerosis: A fully automatic investigation of the magnetic susceptibility in the precentral cortex.

PURPOSE: Diagnostic work-up in motor neuron disease (MND) needs a quantitative biomarker of upper motor neuron (UMN) impairment. We investigated the susceptibility properties of the precentral cortex in a cohort of patients affected by Amyotrophic lateral sclerosis (ALS) to obtain a useful biomarker of UMN impairment in a fully automatic paradigm. MATERIALS AND METHODS: We retrospectively collected imaging and clinical data of 42 ALS patients who had undergone brain 3 T MRI including tridimensional T1-weighted and spoiled gradient-echo multi-echo T2-weighted images. We further acquired images from 23 healthy control (HC) volunteers. The precentral cortex was automatically segmented and the cortical thickness calculated. Histogram metrics (mean, median, standard deviation, skewness, kurtosis) derived from the quantitative susceptibility map (QSM) were extracted from the automatically segmented precentral cortex. Multivariate regression analyses were performed to identify the variables predicting the disease status (ALS vs HC), the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the UMN score. RESULTS: A decreased cortical thickness (B = 9.40; Wald's test = 7.43; p = 0.006) and increased susceptibility skewness (B = -3.08; Wald's test = 4.36; p = 0.037) independently predicted ALS in a logistic regression model (χ2(3, N = 65) = 22.07, p < 0.001. No predictors of ALSFRS-R were identified. An increased susceptibility skewness (ß = 0.55; t = 4.23; p < 0.001) and longer disease duration (ß = 0.35; t = 2.67; p = 0.011) independently predicted a higher UMN score in a linear regression model (R2 = 0.32; p < 0.001). CONCLUSION: The susceptibility skewness might be an unbiased quantitative biomarker of UMN impairment in ALS patients.

Disorders of Ventral Induction/Spectrum of Holoprosencephaly.

Disorders of the ventral induction give rise to a group of congenital malformations that share in common the failure of the prosencephalon cleavage and subsequent formation of midline structures, presenting with a wide spectrum of severity. This article focuses on the imaging findings of the holoprosencephaly spectrum and septo-optic dysplasia, their epidemiology, embryology, and the common clinical associated anomalies. Knowledge of the imaging features of these disorders is necessary for a correct interpretation of findings and accurate parental counseling. Diagnostic evaluation of patients should include molecular screening and genetic counseling to characterize prognosis and risk of recurrence.

Clinical safety of 3-T brain magnetic resonance imaging in newborns.

BACKGROUND: The effects and potential hazards of brain magnetic resonance imaging (MRI) at 3 T in newborns are debated. OBJECTIVE: Assess the impact of 3-T MRI in newborns on body temperature and physiological parameters. MATERIAL AND METHODS: Forty-nine newborns, born preterm and at term, underwent 3-T brain MRI at term-corrected age. Rectal and skin temperature, oxygen saturation and heart rate were recorded before, during and after the scan. RESULTS: A statistically significant increase in skin temperature of 0.6 °C was observed at the end of the MRI scan (P<0.01). There was no significant changes in rectal temperature, heart rate or oxygen saturation. CONCLUSION: Core temperature, heart rate and oxygen saturation in newborns were not affected by 3-T brain MR scanning.

Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review.

The typical presentation of early stage lung cancers on low-dose CT screening are non-calcified pulmonary nodules. However, there is a wide spectrum of unusual focal abnormalities that can be early presentations of lung cancer. These abnormalities include, for example, cancers associated with 'cystic airspaces' or scar-like cancers. The detection of lung cancer with low-dose CT can be affected by the absence of intravenous contrast medium. As a consequence, endobronchial and central lesions can be difficult to recognize, raising the potential for missed cancers. Focal lesions arising within pre-existing lung disease, such as lung fibrosis or apical scars, can also be early lung cancer manifestations and deserve particular consideration as recognition of these lesions may be hindered by the underlying disease. Furthermore, the unpredictable growth rate of lung cancer, which ranges from indolent to aggressive cancers, necessitates attention to the wide spectrum of progression in lung cancer appearance on serial low-dose CT scans. In this pictorial review we discuss the spectrum of early lung cancer presentation in low-dose CT screening, highlighting typical as well as unusual radiological features and the varied growth rates of early lung cancer. Teaching Points • There is a wide spectrum of early presentations of lung cancer on LDCT. • Low radiation dose and the absence of contrast medium injection can affect lung cancer detection. • Lung cancer growth shows various behaviours, ranging from indolent to aggressive cancers. • Familiarity with LDCT technique can improve CT screening effectiveness and avoid missed diagnosis.

Neurodevelopmental outcome at 36 months in very low birth weight premature infants with MR diffuse excessive high signal intensity (DEHSI) of cerebral white matter.

PURPOSE: To understand the meaning of diffuse excessive high signal intensity (DEHSI) of white matter (WM), a frequently observed finding on MR in VLBW infants at a corrected term age. METHODS: This is a retrospective study. Qualitative visual assessment of cerebral WM signal intensity on T2WI was performed by two readers on 78 VLBW infants, scanned on a 1.5 T-MRI at term equivalent age. ADC values were then measured in six regions of interest: four in frontal and parietal periventricular and two in parietal subcortical WM. Mean ADC values were then compared with qualitative visual assessment and with mean ADC values obtained ten term healthy babies. Both periventricular and subcortical mean ADC values were correlated with the neurological follow-up, evaluated with the Griffith's mental developmental scale at 36 months. RESULTS: There was no agreement between the visual qualitative assessment of white matter DEHSI and corresponding ADC values (P values = 0.42 for periventricular WM; P values = 0.18 for subcortical WM). Mean ADC values were higher in preterms than in term babies (P values <0.001). No significant correlation was found between ADC values and the developmental quotient at 36 months (P values >0.05). CONCLUSIONS: DEHSI in VLBW infants is a MR finding poorly defined with conventional T2 MRI. The presence of T2 hyperintensities weakly correlates with ADC, and ADC values are not associated with the neurological long-term outcome at 3 years, demonstrating that DEHSI should not be considered as a WM disease.

Role of CT perfusion in monitoring and prediction of response to therapy of head and neck squamous cell carcinoma.

This review aims to summarize the technique and clinical applications of CT perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments.