Surface-based integration approach for fNIRS-fMRI reliability assessment

Introduction: Studies integrating functional near-infrared spectroscopy (fNIRS) with functional MRI (fMRI) employ heterogeneous methods in defining common regions of interest in which similarities are assessed. Therefore, spatial agreement and temporal correlation may not be reproducible across studies. In the present work, we address this issue by proposing a novel method for integration and analysis of fNIRS and fMRI over the cortical surface. Materials and methods: Eighteen healthy volunteers (age mean±SD 30.55 ± 4.7, 7 males) performed a motor task during non-simultaneous fMRI and fNIRS acquisitions. First, fNIRS and fMRI data were integrated by projecting subject- and group-level source maps over the cortical surface mesh to define anatomically constrained functional ROIs (acfROI). Next, spatial agreement and temporal correlation were quantified as Dice Coefficient (DC) and Pearson's correlation coefficient between fNIRS-fMRI in the acfROIs. Results: Subject-level results revealed moderate to substantial spatial agreement (DC range 0.43 - 0.64), confirmed at the group-level only for blood oxygenation level-dependent (BOLD) signal vs. HbO2 (0.44 - 0.69), while lack of agreement was found for BOLD vs. HbR in some instances (0.05 - 0.49). Subject-level temporal correlation was moderate to strong (0.79 - 0.85 for BOLD vs. HbO2 and -0.62 to -0.72 for BOLD vs. HbR), while an overall strong correlation was found for group-level results (0.95 - 0.98 for BOLD vs. HbO2 and -0.91 to -0.94 for BOLD vs. HbR). Conclusion: The proposed method directly compares fNIRS and fMRI by projecting individual source maps to the cortical surface. Our results indicate spatial and temporal correspondence between fNIRS and fMRI, and promotes the use of fNIRS when more ecological acquision settings are required, such as longitudinal monitoring of brain activity before and after rehabilitation

Cardiac and Respiratory Influences on Intracranial and Neck Venous Flow, Estimated Using Real-Time Phase-Contrast MRI

The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck's venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump's greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage

Brain perfusion patterns: consistency and similarity with fMRI resting state networks and arterial vascular territories

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Measuring respiratory and cardiac influences on blood and cerebrospinal fluid flow with real-time MRI

Background. A link between various pathological conditions and blood and cerebrospinal fluid (CSF) flow alterations has been suggested by numerous studies.1 The blood and CSF dynamics are influenced by many factors, such as posture,2 heart beating, and thoracic pressure changes during respiration.2,3 The blood/CSF can be estimated using phase-contrast (PC) – magnetic resonance imaging (MRI). However, the clinical cardiac-gated cine PC-MRI requires several heartbeats to form the time-resolved flow images covering the entire cardiac cycle, not allowing to assess beat-by-beat variability differences and respiratory-driven flow changes. To overcome these limitations, we recently used a real-time (RT)-PC prototype for the study of blood and CSF flow rate modulations, showing low-frequency oscillations (Mayer waves).4 With the same MRI technique, in the current study we focused on assessing the cardiac and respiratory modulations on the blood and CSF flow rates, and the effects of different respiration modes. Methods. Thirty healthy volunteers (21 females, median age=26 years old, age range= 19-57 years old) were examined with a 3 T scanner. RT-PC sequences (Figure 1) allowed for a quantification of the flow rates of internal carotid arteries (ICAs), internal jugular veins (IJVs), and CSF at the first cervical level. The superior sagittal sinus (SSS) was also studied in 16 subjects.5 The flow rates were estimated with a temporal resolution of 58.5 ms for the blood, and 94 ms for the CSF. Each RT-PC lasted 60 seconds and was repeated three times: while the subject breathed with free (F) breathing, at a constant rate with a normal (PN) or forced (PD) strength. The systolic, diastolic and average flow rates and their power spectral densities were computed. High and very-high frequency peaks were identified on the spectra. Frequencies associated to the identified peaks were compared to the respiratory and cardiac frequencies estimated by a thoracic band and a pulse oximeter. The area under the spectra, normalized by the flow rate variance, was computed in the respiratory and cardiac frequency ranges (0.5 Hz-wide ranges, centered on the cardiac or breathing frequency peaks, respectively). Results. The frequencies associated with the spectral peaks were not significantly different compared to the respiratory and cardiac frequencies, for all regions and breathing modes. The average blood flow rate and the diastolic CSF peak progressively decreased from F to PN to PD breathing, the flow rate variance remained stable, and only the ICAs cross-sectional area decreased. The respiratory modulation increased with PD breathing compared with F and PN, while the cardiac modulations were less predominant for all the structures of interest. Conclusions. Using the RT-PC sequence we showed that the blood and CSF flow rates were modulated at the respiratory and cardiac frequencies. The observed reduced blood flow rate during forced breathing in the arteries and consequently in the extra and intracranial veins are suggestive of compensatory vasoconstriction in response to decreased CO2 blood concentration. Breathing modulation of flow rates was observed both in the extracranial and intracranial compartments, and it was greater during forced breathing than free breathing, due to the greater thoracic pump effect on the flow rates

Multi-centre and multi-vendor reproducibility of a standardized protocol for quantitative susceptibility Mapping of the human brain at 3T

: Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN - Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed. The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005-0.025 ppm, was comparable to the result of the traveling brain experiment. The harmonized QSM protocol of the RIN - Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis

Tecniche ecocardiografiche per lo studio degli effetti cardiotossici della chemioterapia

Scopo della tesi è illustrare l’evoluzione delle tecniche ecocardiografiche relativamente alla diagnosi precoce della cardiotossicità. L’elaborato espone le modalità di imaging ecocardiografico che vengono utilizzate per diagnosticare la cardiotossicità a partire dall’ecocardiografia bidimensionale, fino alle tecniche tridimensionali con acquisizione in tempo reale, attualmente in evoluzione. Si analizzano le varie tecniche diagnostiche rese disponibili dall’esame ecocardiografico: ecocardiografia a contrasto, doppler ad onda continua e pulsata e color doppler, e i metodi e le stime attraverso i quali è possibile quantificare i volumi cardiaci, indici della funzionalità del miocardio. La frazione di eiezione è infatti stata, fino ad ora, il parametro di riferimento per la verifica di lesioni cardiache riportate a seguito di terapia antitumorale. La cardiotossicità viene riscontrata per riduzioni dei valori della frazione di eiezione da ≥5% a <55% con sintomi di scompenso cardiaco e riduzione asintomatica da ≥10% al 55%. Tuttavia, l’osservazione di questo parametro, permette di quantificare il danno riportato quando ormai ha avuto ripercussioni funzionali. In campo clinico, si sta imponendo, al giorno d’oggi, l’analisi delle deformazioni cardiache per una valutazione precoce dell’insorgenza della cardiotossicità. Lo studio delle deformazioni cardiache viene effettuato tramite una nuova tecnica di imaging: l’ecocardiografia speckle tracking (STE), che consente un’analisi quantitativa e oggettiva, poiché indipendente dall’angolo di insonazione, della funzionalità miocardica sia globale sia locale, analizzando le dislocazioni spaziali degli speckles, punti generati dall’interazione tra ultrasuoni e fibre miocardiche. I parametri principali estrapolati dall’indagine sono: deformazione longitudinale, deformazione radiale e deformazione circonferenziale che descrivono la meccanica del muscolo cardiaco derivante dall’anatomia delle fibre miocardiche. La STE sviluppata inizialmente in 2D, è disponibile ora anche in 3D, permettendo la valutazione del vettore delle dislocazioni lungo le tre dimensioni e non più limitatamente ad un piano. Un confronto tra le due mostra come nella STE bidimensionale venga evidenziata una grande variabilità nella misura delle dislocazioni mentre la 3D mostra un pattern più uniforme, coerente con la normale motilità delle pareti cardiache. La valutazione della deformazione longitudinale globale (GLS), compiuta tramite ecocardiografia speckle tracking, viene riconosciuta come indice quantitativo della funzione del ventricolo sinistro le cui riduzioni sono predittive di cardiotossicità. Queste riduzioni vengono riscontrate anche per valori di frazioni di eiezione normale: ne risulta che costituiscono un più efficace e sensibile indicatore di cardiotossicità e possono essere utilizzate per la sua diagnosi precoce

Optimal echo times for quantitative susceptibility mapping: A test-retest study on basal ganglia and subcortical brain nuclei

Quantitative Susceptibility Mapping (QSM) is a recent MRI-technique able to quantify the bulk magnetic susceptibility of myelin, iron, and calcium in the brain. Its variability across different acquisition parameters has prompted the need for standardisation across multiple centres and MRI vendors. However, a high level of agreement between repeated imaging acquisitions is equally important. With this study we aimed to assess the inter-scan repeatability of an optimised multi-echo GRE sequence in 28 healthy volunteers. We extracted and compared the susceptibility measures from the scan and rescan acquisitions across 7 bilateral brain regions (i.e., 14 regions of interest (ROIs)) relevant for neurodegeneration. Repeatability was first assessed while reconstructing QSM with a fixed number of echo times (i.e., 8). Excellent inter-scan repeatability was found for putamen, globus pallidus and caudate nucleus, while good performance characterised the remaining structures. An increased variability was instead noted for small ROIs like red nucleus and substantia nigra. Secondly, we assessed the impact exerted on repeatability by the number of echoes used to derive QSM maps. Results were impacted by this parameter, especially in smaller regions. Larger brain structures, on the other hand, showed more consistent performance. Nevertheless, with either 8 or 7 echoes we managed to obtain good inter-scan repeatability on almost all ROIs. These findings indicate that the designed acquisition/reconstruction protocol has wide applicability, particularly in clinical or research settings involving longitudinal acquisitions (e.g. rehabilitation studies)