Real-Time Phase-Contrast MRI to Monitor Cervical Blood and Cerebrospinal Fluid Flow Beat-by-Beat Variability

Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The arterial (AF), venous (VF), and cerebrospinal fluid (CSF) flow (CSFF) were computed as velocity integrals over the internal carotid artery, internal jugular vein, and CSF. AF, VF, and CSFF signals were segmented in inspiration and expiration beats, to assess the respiration influence. Systolic and diastolic BBV, and heart period series underwent autoregressive power spectral density analysis, to evaluate the low-frequency (LF, Mayer waves) and high frequency (HF, respiratory waves) components. The diastolic VF had the largest BBV. LF power was high in the diastolic AF series, poor in all CSFF series. The pulse wave analyses revealed higher mean amplitude during inspiration. Findings suggests a possible role of LF modulation of IC resistances and propagation of HF waves from VF to AF and CCSF. PC-RT-MRI could provide new insight into the interaction between CV and IC regulation and pave the way for a detailed analysis of the cerebrovascular effects of varied respiration patterns due to exercise and rehabilitation

Comparing resting state fMRI de-noising approaches using multi- and single-echo acquisitions

Artifact removal in resting state fMRI (rfMRI) data remains a serious challenge, with even subtle head motion undermining reliability and reproducibility. Here we compared some of the most popular single-echo de-noising methodsÐregression of Motion parameters, White matter and Cerebrospinal fluid signals (MWC method), FMRIB's ICA-based X-noiseifier (FIX) and ICA-based Automatic Removal Of motion Artifacts (ICA-AROMA)Ðwith a multiecho approach (ME-ICA) that exploits the linear dependency of BOLD on the echo time. Data were acquired using a clinical scanner and included 30 young, healthy participants (minimal head motion) and 30 Attention Deficit Hyperactivity Disorder patients (greater head motion). De-noising effectiveness was assessed in terms of data quality after each cleanup procedure, ability to uncouple BOLD signal and motion and preservation of default mode network (DMN) functional connectivity. Most cleaning methods showed a positive impact on data quality. However, based on the investigated metrics, ME-ICA was the most robust. It minimized the impact of motion on FC even for high motion participants and preserved DMN functional connectivity structure. The high-quality results obtained using ME-ICA suggest that using a multi-echo EPI sequence, reliable rfMRI data can be obtained in a clinical setting

A Novel Approach of Groupwise fMRI-Guided Tractography Allowing to Characterize the Clinical Evolution of Alzheimer's Disease

Guiding diffusion tract-based anatomy by functional magnetic resonance imaging (fMRI), we aim to investigate the relationship between structural connectivity and functional activity in the human brain. To this purpose, we introduced a novel groupwise fMRI-guided tractographic approach, that was applied on a population ranging between prodromic and moderate stages of Alzheimer's disease (AD). The study comprised of 15 subjects affected by amnestic mild cognitive impairment (aMCI), 14 diagnosed with AD and 14 elderly healthy adults who were used as controls. By creating representative (ensemble) functionally guided tracts within each group of participants, our methodology highlighted the white matter fiber connections involved in verbal fluency functions for a specific population, and hypothesized on brain compensation mechanisms that potentially counteract or reduce cognitive impairment symptoms in prodromic AD. Our hope is that this fMRI-guided tractographic approach could have potential impact in various clinical studies, while investigating white/gray matter connectivity, in both health and disease

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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Feasibility of high-frequency percussions in people with severe acquired brain injury and tracheostomy: an observational study

People with severe acquired brain injury (pwSABI) frequently experience pulmonary complications. Among these, atelectasis can occur as a result of pneumonia, thus increasing the chance of developing acute respiratory failure. Respiratory physiotherapy contribution to the management of atelectasis in pwSABI is yet poorly understood. We conducted a retrospective analysis on 15 non-cooperative pwSABI with tracheostomy and spontaneously breathing, hospitalized and treated with high-frequency percussion physiotherapy between September 2018 and February 2021 at the Neurological Rehabilitation Unit of the IRCCS “S.Maria Nascente - Fondazione Don Gnocchi”, Milan. Our primary aim was to investigate the feasibility of such a physiotherapy intervention method. Then, we assessed changes in respiratory measures (arterial blood gas analysis and peripheral night-time oxygen saturation) and high-resolution computed tomography lung images, evaluated before and after the physiotherapy treatment. The radiological measures were a modified radiological atelectasis score (mRAS) assigned by two radiologists, and an opacity score automatically provided by the software CT Pneumonia Analysis® that identifies the regions of abnormal lung patterns. Treatment diaries showed that all treatments were completed, and no adverse events during treatment were registered. Among the 15 pwSABI analyzed, 8 were treated with IPV® and 7 with MetaNeb®. After a median of 14 (I-III quartile=12.5-14.5) days of treatment, we observed a statistical improvement in various arterial blood gas measures and peripheral night-time oxygen saturation measures. We also found radiological improvement or stability in more than 80% of pwSABI. In conclusion, our physiotherapy approach was feasible, and we observed respiratory parameters and radiological improvements. Using technology to assess abnormal tomographic patterns could be of interest to disentangle the short-term effects of respiratory physiotherapy on non-collaborating people

Relationship between cerebrovascular reactivity and age in multiple sclerosis

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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

Determinants of Disability in Multiple Sclerosis: An Immunological and MRI Study

Multiple sclerosis (MS) is characterized by a wide interpatient clinical variability and available biomarkers of disease severity still have suboptimal reliability. We aimed to assess immunological and MRI-derived measures of brain tissue damage in patients with different motor impairment degrees, for in vivo investigating the pathogenesis of MS-related disability. Twenty-two benign (B), 26 secondary progressive (SP), and 11 early, nondisabled relapsing-remitting (RR) MS patients and 37 healthy controls (HC) underwent conventional and diffusion tensor brain MRI and, as regards MS patients, immunophenotypic and functional analysis of stimulated peripheral blood mononuclear cells (PBMC). Corticospinal tract (CST) fractional anisotropy and grey matter volume were lower and CST diffusivity was higher in SPMS compared to RRMS and BMS patients. CD14+IL6+ and CD4+IL25+ cell percentages were higher in BMS than in SPMS patients. A multivariable model having EDSS as the dependent variable retained the following independent predictors: grey matter volume, CD14+IL6+ and CD4+IL25+ cell percentages. In patients without motor impairment after long-lasting MS, the grey matter and CST damage degree seem to remain as low as in the earlier disease stages and an immunological pattern suggestive of balanced pro- and anti-inflammatory activity is observed. MRI-derived and immunological measures might be used as complementary biomarkers of MS severity

An anatomy-based lumped parameter model of cerebrospinal venous circulation: can an extracranial anatomical change impact intracranial hemodynamics?

Background The relationship between extracranial venous system abnormalities and central nervous system disorders has been recently theorized. In this paper we delve into this hypothesis by modeling the venous drainage in brain and spinal column areas and simulating the intracranial flow changes due to extracranial morphological stenoses. Methods A lumped parameter model of the cerebro-spinal venous drainage was created based on anatomical knowledge and vessels diameters and lengths taken from literature. Each vein was modeled as a hydraulic resistance, calculated through Poiseuille’s law. The inputs of the model were arterial flow rates of the intracranial, vertebral and lumbar districts. The effects of the obstruction of the main venous outflows were simulated. A database comprising 112 Multiple Sclerosis patients (Male/Female = 42/70; median age ± standard deviation = 43.7 ± 10.5 years) was retrospectively analyzed. Results The flow rate of the main veins estimated with the model was similar to the measures of 21 healthy controls (Male/Female = 10/11; mean age ± standard deviation = 31 ± 11 years), obtained with a 1.5 T Magnetic Resonance scanner. The intracranial reflux topography predicted with the model in cases of internal jugular vein diameter reduction was similar to those observed in the patients with internal jugular vein obstacles. Conclusions The proposed model can predict physiological and pathological behaviors with good fidelity. Despite the simplifications introduced in cerebrospinal venous circulation modeling, the key anatomical feature of the lumped parameter model allowed for a detailed analysis of the consequences of extracranial venous impairments on intracranial pressure and hemodynamics