Biology subjects

Duffin, J.

Publications and source records attributed to Duffin, J..

4 recordsLinked to original sources

bioRxiv2024

Cerebral perfusion metrics calculated directly, model-free, from a hypoxia-induced step change in deoxyhemoglobin

Dynamic susceptibility contrast (DSC) perfusion MRI measures blood flow metrics via application of a BOLD pulse sequence during transit of a gadolinium-based contrast agent (GBCA), We have previously shown that can also be performed using endogenous deoxyhemoglobin (dOHb) as a replacement for GBCA since dOHb also has the necessary paramagnetic properties similar to GBCA 1. Conventional analysis with these contrast agents includes deconvolution of an arterial input function (AIF) assuming a kinetic model. However, the immediate decrease in dOHb that occurs during reoxygenation from a transient hypoxia constitutes a step reduction in susceptibility that permits direct, model-free, calculation of relative resting perfusion metrics. The metrics from this step analysis for seven healthy volunteers were compared to those from a conventional analysis of GBCA and dOHb. Voxel- wise maps of mean transit time, and relative cerebral blood flow and cerebral blood volume, had a high spatial congruence for all three analyses and were similar in appearance to published maps. The time course of the T2*-weighted signal step response identifies both the arrival time, the distribution of the step increase in arterial oxygen saturation, SaO2, and the voxel filling phase. The analysis of a step change in dOHb during rapid reoxygenation is an alternative way of calculating perfusion metrics directly from measurements of the resulting T2*-weighted signal, avoiding the potential errors from the use of a kinetic model and requirement for selection of an AIF.

neuroscience↗

bioRxiv2022

Perfusion Quantification in the Human Brain Using DSC MRI - Simulations and Validations at 3T

Gadolinium (Gd) and deoxyhemoglobin (dOHb) are paramagnetic contrast agents capable of inducing changes in T2*-weighted MRI signal, utilized in dynamic susceptibility contrast (DSC) MRI. With multiple contrast agents and analysis choices, there are a variety of questions as to its capability to accurately quantify perfusion values. To address these questions, we developed a novel signal model for DSC MRI that incorporates signal contributions from intravascular and extravascular water proton spins at 3T for arterial, venous, and cerebral tissue voxels. This framework allowed us to model the MRI signal in response to changes in Gd and dOHb concentrations, and the effects that various experimental and tissue parameters have on perfusion quantification. We compared the predictions of the numerical simulations with those obtained from experimental data at 3T on six healthy human subjects using Gd and dOHb boluses as contrast agents. Using standard DSC analysis, we identified perfusion quantification dependencies in the experimental results that were in close agreement with the simulations. We found that a reduced baseline oxygen saturation (base-SaO2), greater susceptibility of applied contrast agent (Gd vs dOHb), and larger magnitude of the hypoxic drop ({Delta}SaO2) reduces overestimation of the cerebral blood volume (rCBV) and flow (rCBF). Furthermore, shortening the bolus duration increases the accuracy and reduces the calculated values of mean transit time (MTT). This study demonstrates that changes in Gd and dOHb can be described by the same unifying theoretical framework, as validated by the experimental results. Based on our work, we suggest practices in DSC MRI that increase accuracy and reduce inter- and intra-subject variability. In uncovering a wide array of quantification dependencies, we argue that caution must be exercised when comparing perfusion values obtained from a standard DSC MRI analysis when employing different experimental paradigms.

biophysics↗

bioRxiv2022

Quantifying cerebral blood arrival times using hypoxia-mediated arterial BOLD contrast

Cerebral blood arrival and tissue transit times are sensitive measures of the efficiency of tissue perfusion and can provide clinically meaningful information on collateral blood flow status. We exploit the arterial blood oxygen level dependent (BOLD) signal contrast established by precisely modulating arterial hemoglobin saturation using hypoxic respiratory challenges (dOHb-BOLD) to quantify arterial blood arrival times throughout the brain. A combination of hemodynamic lag with a modified carpet plot analysis yielded lag, onset (blood arrival), mean transit time (MTT) and hypoxic response information, which is indicative of relative total blood volume. Onset times averaged across 12 healthy subjects were 1.1 {+/-} 0.4 and 1.9 {+/-} 0.6 for cortical gray and deep white matter, respectively. The average whole brain MTT was 4.5 {+/-} 0.9 seconds. The dOHb-BOLD response was 1.7 fold higher in grey versus white; in line with known differences in regional blood volume fraction. Our method was also applied in unilateral carotid artery occlusion patient, which revealed prolonged signal onset with normal perfusion in the affected hemisphere. In cases with exhausted reserve capacity or confounding flow effects such as vascular steal, dOHb-BOLD can potentially inform on collateral flow pathways to provide a valuable compliment to clinical vascular reactivity measures.

neuroscience↗

bioRxiv2021

Cerebral perfusion imaging: Hypoxia-induced deoxyhemoglobin or gadolinium?

Assessment of resting cerebrovascular perfusion measures (mean transit time, cerebral blood flow and cerebral blood volume) with magnetic resonance imaging currently requires the intravascular injection of the dynamic susceptibility contrast agent gadolinium. An initial comparison between hypoxia-induced deoxyhemoglobin and gadolinium was made for these measures in six healthy participants. A bolus of deoxyhemoglobin is generated in the lung via transient hypoxia induced by an available computer-controlled gas blender technology employing sequential gas delivery (RespirAct). We hypothesised and confirmed perfusion measures from both susceptibility contrast agents would yield similar spatial patterns of cerebrovascular perfusion measures. We conclude that hypoxia-induced deoxyhemoglobin, an endogenously, non-invasively generated, non-allergenic, non-toxic, recyclable, environmentally innocuous molecule, may be suitable to become the first new magnetic resonance imaging susceptibility contrast agent introduction since gadolinium.

neuroscience↗