Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

Biondetti, Emma; Chiarelli, Antonio Maria; Germuska, Michael; Lipp, Ilona; Villani, Alessandro; Caporale, Alessandra S.; Patitucci, Eleonora; Murphy, Kevin; Tomassini, Valentina; Wise, Richard G.

doi:10.1016/j.neuroimage.2023.120492

Cited by 3 publications

(2 citation statements)

References 61 publications

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“…For the same reason, we suggest that using RSF metrics for rescaling task activation values might not truly rescale the signal based on vascular changes, rather than on features of the neurovascular coupling and the haemodynamic response (Bailes et al, 2023). Instead, it has also been suggested that the BOLD signal changes induced by the vasodilation associated to breath-holds is strongly influenced by changes in cerebral blood volume (CBV) characterised by deoxy-haemoglobin, and that a novel new marker of deoxygenated CBV with BOLD (BOLD-CBV) can account for more between-subject variability in task-induced BOLD responses (Biondetti et al, 2024).…”

Section: Discussionmentioning

confidence: 99%

Individual variability in the relationship between physiological and resting-state fMRI metrics

Moia,

Chen,

Uruñuela

et al. 2024

Preprint

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Cerebrovascular Reactivity (CVR), the brain's vascular response to a vasodilatory stimulus, can be measured using fMRI during breathing challenges that modulate arterial CO2levels. CVR is an important indicator of cerebrovascular health, although its estimation can be challenging due to the extra experimental setup and/or the subject compliance required. To overcome these limitations, summary metrics based on resting state fluctuations (RSF), such as the (fractional) amplitude of low frequency fluctuations (f/ALFF) and the resting state fluctuation amplitude (RSFA), have been proposed as alternative estimates of CVR, as they are frequently associated with vascular and physiological factors. Previous studies have reported a significant relationship between CVR estimates obtained by means of respiratory paradigms and RSF metrics. However, the total sample sizes, considering both subjects and sessions, are typically small, and not all studies agree on the degree of the relationship. Furthermore, to our knowledge, these studies have only reported cross-sectional analyses, whereas intra-subject longitudinal relationships between CVR estimates and RSF metrics are unknown. Leveraging a unique dense sampling dataset in which resting state and breath-hold multi-echo fMRI were collected in 7 subjects with 10 sessions each, we provide evidence of high individual variability in the inter-session (i.e. intra-subject) relationship between RSF metrics and CVR. These results indicate that RSF metrics might not be a suitable proxy of CVR in clinical settings or for BOLD signal calibration as they may not properly account for intra-individual physiological variations in BOLD fMRI data.

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Section: Discussionmentioning

confidence: 99%

Individual variability in the relationship between physiological and resting-state fMRI metrics

Moia,

Chen,

Uruñuela

et al. 2024

Preprint

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“…Given these inherent mechanistic differences, and the fact that a physiological challenge is being used to assess baseline perfusion, the use of hypercapnia for DSC relies on certain assumptions, including the constancy of oxygen metabolism, and most importantly, the ability to measure an arterial input function (AIF), which represents the input time course of contrast agent, or in this case, vasodilatory agent (see Discussion). Although it may seem counterintuitive to measure baseline perfusion using a physiological challenge (i.e., hypercapnia), it should be noted that previous works within cognitive neuroscience have employed vascular challenges to normalize blood oxygenation level-dependent (BOLD)-based estimates of neuronal activity to venous CBV 4 , 22 (see also calibrated BOLD ‘M’ parameter, which scales with baseline CBV and is calculated using hypercapnic calibration 23 ).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive perfusion MR imaging of the human brain via breath-holding

Schulman,

Kashyap,

Kim

et al. 2024

Sci Rep

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Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3 T and 7 T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3 T vs. 8.5 at 7 T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20–40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

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Non-Invasive Perfusion MR Imaging of the Human Brain via Breath-Holding

Schulman,

Kashyap,

Kim

et al. 2023

Preprint

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Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but the technique’s reliance on gadolinium, an intravascularly injected metal, presents a major limitation. Here, we determined the feasibility of using breath-holds to non-invasively induce DSC perfusion contrast. To achieve this, we acquired T2*-weighted MRI data at both 3T and 7T from ten healthy participants who engaged in eight consecutive breath-holds (16 s each separated by 44 s of rest). By pairing a novel arterial input function with a standard DSC MRI analysis, we successfully quantified essential perfusion parameters, including the cerebral blood volume, flow, and transit delay, and found these perfusion values to be congruent with those documented in the literature using gadolinium. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3Tvs8.5 at 7T) and gray matter-to-white matter contrast at higher field strength. For the first time, we have demonstrated the feasibility of DSC using breath-holds—we are confident that this method holds major promise, both clinically and in research, effectively circumventing the need for invasive contrast agents, particularly at ultra-high field strength.

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Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

Cited by 3 publications

References 61 publications

Individual variability in the relationship between physiological and resting-state fMRI metrics

Individual variability in the relationship between physiological and resting-state fMRI metrics

Non-invasive perfusion MR imaging of the human brain via breath-holding

Non-Invasive Perfusion MR Imaging of the Human Brain via Breath-Holding

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