MRI evidence for altered venous drainage and intracranial compliance in mild traumatic brain injury.

To compare venous drainage patterns and associated intracranial hydrodynamics between subjects who experienced mild traumatic brain injury (mTBI) and age- and gender-matched controls. Thirty adult subjects (15 with mTBI and 15 age- and gender-matched controls) were investigated using a 3T MR scanner. Time since trauma was 0.5 to 29 years (mean 11.4 years). A 2D-time-of-flight MR-venography of the upper neck was performed to visualize the cervical venous vasculature. Cerebral venous drainage through primary and secondary channels, and intracranial compliance index and pressure were derived using cine-phase contrast imaging of the cerebral arterial inflow, venous outflow, and the craniospinal CSF flow. The intracranial compliance index is the defined as the ratio of maximal intracranial volume and pressure changes during the cardiac cycle. MR estimated ICP was then obtained through the inverse relationship between compliance and ICP. Compared to the controls, subjects with mTBI demonstrated a significantly smaller percentage of venous outflow through internal jugular veins (60.9±21% vs. controls: 76.8±10%; p = 0.01) compensated by an increased drainage through secondary veins (12.3±10.9% vs. 5.5±3.3%; p<0.03). Mean intracranial compliance index was significantly lower in the mTBI cohort (5.8±1.4 vs. controls 8.4±1.9; p<0.0007). Consequently, MR estimate of intracranial pressure was significantly higher in the mTBI cohort (12.5±2.9 mmHg vs. 8.8±2.0 mmHg; p<0.0007). mTBI is associated with increased venous drainage through secondary pathways. This reflects higher outflow impedance, which may explain the finding of reduced intracranial compliance. These results suggest that hemodynamic and hydrodynamic changes following mTBI persist even in the absence of clinical symptoms and abnormal findings in conventional MR imaging

Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures

Blood-flow models of the circle of Willis from magnetic resonance data

Detailed knowledge of the cerebral hemodynamics is important for a variety of clinical applications. Cerebral perfusion depends not only on the status of the diseased vessels but also on the patency of collateral pathways provided by the circle of Willis. Due to the large anatomical and physiologic variability among individuals, realistic patient-specific models can provide new insights into the cerebral hemodynamics. This paper presents an image-based methodology for constructing patient-specific models of the cerebral circulation. This methodology combines anatomical and physiologic imaging techniques with computer simulation technology. The methodology is illustrated with a finite element model constructed from magnetic resonance image data of a normal volunteer. Several of the remaining challenging problems are identified. This work represents a starting point in the development of realistic models that can be applied to the study of cerebrovascular diseases and their treatment

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

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

Brain arterial diameters and cognitive performance: the Northern Manhattan Study

Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia

Differential Effect of Left vs. Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study

Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right white matter hyperintensity volume (WMHV) asymmetry was associated with functional trajectories.Methods: In the Northern Manhattan Study, participants underwent brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0–100) over a mean of 7.3 years. Generalized estimating equations (GEE) models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up.Results: Among 1,195 participants, greater WMHV asymmetry in the parietal lobes (−8.46 BI points per unit greater WMHV on the right compared to left, 95% CI −3.07, −13.86) and temporal lobes (−2.48 BI points, 95% CI −1.04, −3.93) was associated with lower overall function. Greater WMHV asymmetry in the parietal lobes (−1.09 additional BI points per year per unit greater WMHV on the left compared to right, 95% CI −1.89, −0.28) was independently associated with accelerated functional decline.Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional status

Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1. Technical Efficacy: Stage 3

Poor sleep is associated with smaller hippocampal subfields in cognitively normal elderly individuals

Background Sleep quality decreases in normal aging and is manifested in neurodegenerative diseases including Alzheimer’s disease (AD). Hippocampus is a critical structure for brain health and plays a major role in memory. Although recent studies have demonstrated that reduced hippocampal volume is associated with poor sleep quality, the relationship between sleep quality and volumes of hippocampal subfields (HSs) remains unknown. The objective of this study is to investigate associations between self‐reported sleep quality measures and HS volumes in cognitively normal elderly individuals. Method Sixty‐seven cognitively normal elderly individuals aged 60 to 83 years with self‐reported Pittsburgh Sleep Quality Index (PSQI) were classified into two groups: 30 normal sleepers with PSQI < 5 and 37 poor sleepers with PSQI ≥5. The two groups were equivalent in terms of age, gender, ethnicity, education, handedness and cognitive performance. HSs were segmented in very high resolution T2‐weighted MRI sequence (with an in‐plane resolution of 0.4×0.4 mm2 and 2 mm slice thickness) using the automatic segmentation of hippocampal subfields (ASHS) tool. The HS Volumes were normalized with respect to intracranial volumes. We compared HS volumes between subjects with normal and poor sleep quality. Furthermore, we evaluated associations between the HS volumes and different sleep quality measures, and between the HS volumes and performance of different cognitive tests. Result Compared to normal sleepers, poor sleepers exhibited lower normalized volumes in the left cornu ammonis field 1 (CA1) (p=0.020), dentate gyrus (DG) (p=0.008) and subiculum (p=0.018). Global PSQI was significantly and negatively associated with the normalized volumes of the left CA1 (r=‐0.266), left DG (r=‐0.295) and left subiculum (r=‐0.276). Sleep duration was significantly associated with normalized volumes of the bilateral CA1 (left: r=0.428, right: r=0.438), DG (left: r=0.381, right: r=0.367), left CA2 (r=0.231) and subiculum (r=0.219). Verbal memory scores were associated with the normalized volumes of left CA1 (r=0.382). Conclusion We found association between poor sleep quality and volume decreases in multiple HSs. Improving overall sleep quality, especially sleep duration, could prevent or slow volume loss of the HSs, which are associated with cognitive decline and onset of mild cognitive impairment (MCI) and AD

Self‐reported poor sleep accelerates hippocampal volume loss in cognitively normal healthy elderly

Background Poor sleep quality is a known risk factor for the development of Alzheimer’s disease (AD). However, minimal data is available on the rate of brain tissue volume loss related to self‐reported poor sleep. Our previous cross‐sectional study in cognitively normal elderly adults age 60 and over, demonstrated that poor sleepers exhibited significantly smaller volumes, approximately 7%, in the bilateral hippocampi, superior parietal lobules and left amygdala and smaller cortical thicknesses, over 3%, in the right superior frontal, medial orbitofrontal cortices and frontal pole, compared to normal sleepers (Alperin et al, 2019). Current study is a follow‐up longitudinal investigation comparing rates of tissue loss in these brain regions of interest (ROIs) between elderly good and poor sleepers with normal cognition. Method Forty‐eight cognitively normal elderly individuals age 60 to 92 years were classified into two groups: 23 normal sleepers with self‐reported Pittsburgh Sleep Quality Index (PSQI) < 5 and 25 poor sleepers with PSQI ≥ 5. The two groups were equivalent in terms of age, gender, years of education and white matter hyperintensity (WMH) load. The volumes and thickness of the ROIs were measured at baseline and at follow‐up scans to assess rates of tissue loss using FreeSurfer software. Rates of tissue loss over 2 years were compared between two groups. Result No significant association was found between sleep quality, WMH load and rates of thickness loss. Compared to normal sleepers, poor sleepers exhibited 2.8 times higher rates of volume loss in the hippocampus, and 3.3 times higher rate in the posterior cingulate. Global PSQI at baseline was significantly and negatively associated with rates of volume loss in the right hippocampus (rs=‐0.33) and right posterior cingulate cortex (rs=‐0.47). Scores in verbal memory was negatively associated with rates of volume loss in the right hippocampus (r≥0.388). Conclusion Poor sleep quality is associated with significantly accelerated volume loss in the hippocampus and the posterior cingulate cortex in cognitively normal elderly individuals. Intervention for improving sleep quality should be highly considered in cognitively normal elderly adults to delay onset of cognitive impairment and onset of AD