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Background: In patients with chronic coronary syndromes (CCS), increased ventilation/carbon dioxide production ( V ̇ E/ V ̇ CO2) slope has been found to predict disease progression and mortality, similarly to patients with heart failure (HF); however, increased chemosensitivity, a well-established predictor for mortality in patients with HF, has rarely been assessed in patients with CCS. Method: Patients with CCS, HF with reduced ejection fraction (EF < 50%), healthy controls (45+ years), and young healthy adults (<35 years) were recruited. For patients, a V ̇ E/ V ̇ CO2 slope ≥36 was an inclusion criterion. The Duffin rebreathing method was used to determine the resting end-expiratory partial pressure of carbon dioxide (PETCO2), ventilatory recruitment threshold (VRT), and slope (sensitivity) during a hyperoxic (150 mmHg O2) and hypoxic (50 mmHg O2) rebreathing test to determine the central and peripheral chemosensitivity. Results: In patients with CCS, HF, controls, and young healthy adults, median V ̇ E/ V ̇ CO2 slopes were 40.2, 41.3, 30.5, and 28.0, respectively. Both patient groups had similarly reduced hyperoxic VRT (at PETCO2 42.1 and 43.2 mmHg) compared to 46.0 and 48.8 mmHg in the control and young healthy adults. Neither hypoxic VRT nor hyper- or hypoxic slopes were significantly different in patients compared to controls. Both patient groups had lower resting PETCO2 than controls, but only patients with HF had increased breathing frequency and rapid shallow breathing at rest. Conclusion: In patients with HF and/or CCS and excess ventilation, central chemoreflex VRT was reduced independently of the presence of HF. Low VRTs were related to resting excess ventilation in patients with CCS or HF; however, rapid shallow breathing at peak exercise was present only in patients with HF. Clinical trial registration number: NCT05057884. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular reactivity (CVR) is a measure of the change in cerebral blood flow (CBF) in response to a vasoactive challenge. It is a useful indicator of the brain's vascular health. Purpose: To evaluate the factors that influence successful and unsuccessful CVR examinations using precise arterial and end‐tidal partial pressure of CO2 control during blood oxygen level–dependent (BOLD) MRI. Study Type: Retrospective. Subjects: Patients that underwent a CVR between October 2005 and May 2021 were studied (total of 1162 CVR examinations). The mean (±SD) age was 46.1 (±18.8) years, and 352 patients (43%) were female. Field Strength/Sequence: 3 T; T1‐weighted images, T2*‐weighed two‐dimensional gradient‐echo sequence with standard echo‐planar readout. Assessment: Measurements were obtained following precise hypercapnic stimuli using BOLD MRI as a surrogate of CBF. Successful CVR examinations were defined as those where: 1) patients were able to complete CVR testing, and 2) a clinically useful CVR map was generated. Unsuccessful examinations were defined as those where patients were not able to complete the CVR examination or the CVR maps were judged to be unreliable due to, for example, excessive head motion, and poor PETCO2 targeting. Statistical Analysis: Successful and unsuccessful CVR examinations between hypercapnic stimuli, and between different patterns of stimulus were compared with Chi‐Square tests. Interobserver variability was determined by using the intraclass correlation coefficient (P < 0.05 is significant). Results: In total 1115 CVR tests in 662 patients were included in the final analysis. The success rate of generating CVR maps was 90.8% (1012 of 1115). Among the different hypercapnic stimuli, those containing a step plus a ramp protocol was the most successful (95.18%). Among the unsuccessful examinations (9.23%), most were patient related (89.3%), the most common of which was difficulty breathing. Data Conclusion: CO2‐BOLD MRI CVR studies are well tolerated with a high success rate. Evidence Level: 4 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Introduction Controlling the partial pressure of carbon dioxide (PaCO 2) is an important consideration in patients with intracranial steno-occlusive disease to avoid reductions in critical perfusion from vasoconstriction due to hypocapnia, or reductions in blood flow due to steal physiology during hypercapnia. However, the normal range for resting PCO 2 in this patient population is not known. Therefore, we investigated the variability in resting end-tidal PCO 2 (P ET CO 2) in patients with intracranial steno-occlusive disease and the impact of revascularization on resting P ET CO 2 in these patients. Setting and Design Tertiary care center, retrospective chart review Materials and Methods We collected resting P ET CO 2 values in adult patients with intracranial steno-occlusive disease who presented to our institution between January 2010 and June 2021. We also explored postrevascularization changes in resting P ET CO 2 in a subset of patients. Results Two hundred and twenty-seven patients were included [moyamoya vasculopathy (n = 98) and intracranial atherosclerotic disease (n = 129)]. In the whole cohort, mean ± standard deviation resting P ET CO 2 was 37.8 ± 3.9 mm Hg (range: 26–47). In patients with moyamoya vasculopathy and intracranial atherosclerotic disease, resting P ET CO 2 was 38.4 ± 3.6 mm Hg (range: 28–47) and 37.4 ± 4.1 mm Hg (range: 26–46), respectively. A trend was identified suggesting increasing resting P ET CO 2 after revascularization in patients with low preoperative resting P ET CO 2 (<38 mm Hg) and decreasing resting P ET CO 2 after revascularization in patients with high preoperative resting P ET CO 2 (>38 mm Hg). Conclusion This study demonstrates that resting P ET CO 2 in patients with intracranial steno-occlusive disease is highly variable. In some patients, there was a change in resting P ET CO 2 after a revascularization procedure. [ABSTRACT FROM AUTHOR]

Background: Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors. Methods: A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI. Results: Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps. Conclusion: Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Physiology titled "Measuring resting cerebral perfusion using magnetic resonance imaging (MRI)." The editorial discusses the importance of measuring cerebral perfusion metrics, such as cerebral blood flow (CBF), in assessing cerebrovascular health. It highlights the use of magnetic resonance imaging (MRI) as a non-invasive technique for measuring perfusion metrics and discusses various methods and techniques for obtaining accurate measurements. The editorial also emphasizes the interplay between cerebral perfusion and brain metabolic processes and the potential for using advanced physiological MRI in routine clinical practice. [Extracted from the article]

Normobaric hyperoxia stimulates ventilation (V_ E) in a time- and dose-dependent manner. Whether this occurs via an oxygen (O2)-specific mechanism or secondary to carbon dioxide (CO2) retention at the central chemoreceptors remains unclear. We measured the ventilatory response to hyperoxic CO2 rebreathing with O2 clamped at increasingly higher pressures. We hypothesized that the V_ E versus PCO2 relationship is fixed and independent of PO2. On four occasions, 20 participants (10 F; mean ± SD age: 24 ± 4 yr) performed three repetitions of modified rebreathing in four, randomized, isoxic-hyperoxic conditions: mild: PO2=150 mmHg; moderate: PO2=200 mmHg; high: PO2=300 mmHg; and extreme: PO2-700 mmHg. Breath-by-breath V_ E, end-tidal CO2 (PETCO2), and O2 (PETO2) were measured by pneumotach and gas analyzer. For each rebreathing trial, the PETCO2 at which V_ E rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V_ E (V_ EBSL, L·min-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V_ ES, L·min-1·mmHg-1). For each condition, VRT, V_ EBSL, and V_ ES from liketrials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of PETO2 on V_ EBSL (mild: 7.4 ± 4.2 L·min-1; moderate: 6.9 ± 4.2 L·min-1; high: 6.5±3.7 L·min-1; extreme: 7.5 ± 2.7 L·min-1; P = 0.24), VRT (mild: 42.8 ± 3.2 mmHg; moderate: 42.5 ± 2.7 mmHg; high: 42.3 ± 2.7 mmHg; extreme: 41.8 ± 2.7 mmHg; P = 0.07), or V_ ES (mild: 4.88±2.6 L·min-1·mmHg-1; moderate: 4.76 ± 2.2 L·min-1·mmHg-1; high: 4.81±2.3 L·min-1·mmHg-1; extreme: 4.39 ± 1.9 L·min-1·mmHg-1; P = 0.41). The V_ E-PCO2 relationship is unaltered across a range of mild to extreme PO2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity. [ABSTRACT FROM AUTHOR]

How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious. We measured the peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic CO2 tensions (PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) to determine the form of the relationship between PChS and central PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$. Twenty participants (10F) completed three repetitions of modified rebreathing tests with end‐tidal PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$) clamped at 150, 70, 60 and 45 mmHg. End‐tidal PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$), PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$, ventilation (V̇$\dot{V}$E) and calculated oxygen saturation (SCO2) were measured breath‐by‐breath by gas‐analyser and pneumotach. The V̇$\dot{V}$E–PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship of repeat‐trials were linear‐interpolated, combined, averaged into 1 mmHg bins, and fitted with a double‐linear function (V̇$\dot{V}$ES, L min−1mmHg−1). PChS was computed at intervals of 1 mmHg of PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ as follows: the difference in V̇$\dot{V}$E between the three hypoxic profiles and the hyperoxic profile (∆V̇$\dot{V}$E) was calculated; three ∆V̇$\dot{V}$E values were plotted against corresponding SCO2; and linear regression determined PChS (Lmin−1mmHg−1%SCO2−1). These processing steps were repeated at each PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ to produce the PChS vs. isocapnic PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship. These were fitted with linear and polynomial functions, and Akaike information criterion identified the best‐fit model. One‐way repeated measures analysis of variance assessed between‐condition differences. V̇$\dot{V}$ES increased (P < 0.0001) with isoxic PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ from 3.7 ± 1.5 L min−1mmHg−1 at 150 mmHg to 4.4 ± 1.8, 5.0 ± 1.6 and 6.0 ± 2.2 Lmin−1mmHg−1 at 70, 60 and 45 mmHg, respectively. Mean SCO2 fell progressively (99.3 ± 0%, 93.7 ± 0.1%, 90.4 ± 0.1% and 80.5 ± 0.1%; P < 0.0001). In all individuals, PChS increased with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$, and this relationship was best described by a linear model in 75%. Despite increasing central chemoreflex activation, PChS increased linearly with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ indicative of an additive central–peripheral chemoreflex response. Key points: How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious.We measured peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic carbon dioxide tensions (PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) to determine the form of the relationship between PChS and central PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$.Participants performed three repetitions of modified rebreathing with end‐tidal PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fixed at 150, 70, 60 and 45 mmHg. PChS was computed at intervals of 1 mmHg of end‐tidal PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$) as follows: the difference in V̇$\dot{V}$E between the three hypoxic profiles and the hyperoxic profile (∆V̇$\dot{V}$E) was calculated; three ∆V̇$\dot{V}$E values were plotted against corresponding calculated oxygen saturation (SCO2); and linear regression determined PChS (Lmin−1mmHg−1%SCO2−1).In all individuals, PChS increased with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$, and this relationship was best described by a linear (rather than polynomial) model in 15 of 20.Most participants did not exhibit a hypo‐ or hyper‐additive effect of central chemoreceptors on the peripheral chemoreflex indicating that the interaction was additive. [ABSTRACT FROM AUTHOR]

Cerebrovascular Reactivity (CVR) is a provocative test used with Blood oxygenation level-dependent (BOLD) Magnetic Resonance Imaging (MRI) studies, where a vasoactive stimulus is applied and the corresponding changes in the cerebral blood flow (CBF) are measured. The most common clinical application is the assessment of cerebral perfusion insufficiency in patients with steno-occlusive disease (SOD). Globally, millions of people suffer from cerebrovascular diseases, and SOD is the most common cause of ischemic stroke. Therefore, CVR analyses can play a vital role in early diagnosis and guiding clinical treatment. This study develops a convolutional neural network (CNN)-based clinical decision support system to facilitate the screening of SOD patients by discriminating between healthy and unhealthy CVR maps. The networks were trained on a confidential CVR dataset with two classes: 68 healthy control subjects, and 163 SOD patients. This original dataset was distributed in a ratio of 80%-10%-10% for training, validation, and testing, respectively, and image augmentations were applied to the training and validation sets. Additionally, some popular pre-trained networks were imported and customized for the objective classification task to conduct transfer learning experiments. Results indicate that a customized CNN with a double-stacked convolution layer architecture produces the best results, consistent with expert clinical readings. [ABSTRACT FROM AUTHOR]

The assessment of resting perfusion measures (mean transit time, cerebral blood flow, and cerebral blood volume) with magnetic resonance imaging currently requires the presence of a susceptibility contrast agent such as gadolinium. Here, we present an initial comparison between perfusion measures obtained using hypoxia‐induced deoxyhemoglobin and gadolinium in healthy study participants. We hypothesize that resting cerebral perfusion measures obtained using precise changes of deoxyhemoglobin concentration will generate images comparable to those obtained using a clinical standard, gadolinium. Eight healthy study participants were recruited (6F; age 23–60). The study was performed using a 3‐Tesla scanner with an eight‐channel head coil. The experimental protocol consisted of a high‐resolution T1‐weighted scan followed by two BOLD sequence scans in which each participant underwent a controlled bolus of transient pulmonary hypoxia, and subsequently received an intravenous bolus of gadolinium. The resting perfusion measures calculated using hypoxia‐induced deoxyhemoglobin and gadolinium yielded maps that looked spatially comparable. There was no statistical difference between methods in the average voxel‐wise measures of mean transit time, relative cerebral blood flow and relative cerebral blood volume, in the gray matter or white matter within each participant. We conclude that perfusion measures generated with hypoxia‐induced deoxyhemoglobin are spatially and quantitatively comparable to those generated from a gadolinium injection in the same healthy participant. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?We assessed the test–retest variability of respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation.What is the main finding and its importance?Modified rebreathing is a reproducible method to characterize responses of central and peripheral respiratory chemoreflexes. Signal averaging of multiple repeated tests minimizes within‐ and between‐test variability, improves the confidence of chemoreflex characterization and reduces the minimal change in parameters required to establish an effect. Future experiments that apply this method might benefit from signal averaging to improve its discriminatory effect. We assessed the test–retest variability of central and peripheral respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. Over four laboratory visits, 13 participants (mean ± SD age, 25 ± 5 years) performed six repetitions of modified rebreathing in isoxic–hypoxic conditions [end‐tidal PO2${P_{{{\rm{O}}_{\rm{2}}}}}$ (PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$) = 50 mmHg] and isoxic–hyperoxic conditions (PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ = 150 mmHg). End‐tidal PCO2${P_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ (PET,CO2${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$), PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ and minute ventilation (V̇$\dot {\rm V}$E) were measured breath‐by‐breath, by gas analyser and pneumotachograph. The V̇$\dot {\rm V}$E versus PET,CO2${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$ relationships were fitted with a piecewise model to estimate the ventilatory recruitment threshold (VRT) and the slope above the VRT (V̇$\dot {\rm V}$ES). Breath‐by‐breath data from the three within‐ and between‐day trials were averaged using two approaches [simple average (fit then average) and ensemble average (average then fit)] and compared with a single‐trial fit. Variability was assessed by intraclass correlation (ICC) and coefficient of variance (CV), and the minimal detectable change was computed for each approach using two independent sets of three trials. Within days, the VRT and V̇$\dot {\rm V}$ES exhibited excellent test–retest variability in both hyperoxic conditions (VRT: ICC = 0.965, CV = 2.3%; V̇$\dot {\rm V}$ES: ICC = 0.932, CV = 15.5%) and hypoxic conditions (VRT: ICC = 0.970, CV = 2.9%; V̇$\dot {\rm V}$ES: ICC = 0.891, CV = 17.2%). Between‐day reproducibility was also excellent (hyperoxia, VRT: ICC = 0.930, CV = 2.2%; V̇$\dot {\rm V}$ES: ICC = 0.918, CV = 14.2%; and hypoxia, VRT: ICC = 0.940, CV = 3.0%; V̇$\dot {\rm V}$ES: ICC = 0.880, CV = 18.1%). Compared with a single‐trial fit, there were no differences in VRT or V̇$\dot {\rm V}$ES using the simple average or ensemble average approaches; however, ensemble averaging reduced the minimal detectable change for V̇$\dot {\rm V}$ES from 2.95 to 1.39 L min−1 mmHg−1 (hyperoxia) and from 3.64 to 1.82 L min−1 mmHg−1 (hypoxia). Single trials of modified rebreathing are reproducible; however, signal averaging of repeated trials improves confidence in parameter estimation. [ABSTRACT FROM AUTHOR]

In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno‐occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high‐resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO2 (PETCO2). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three‐way ANOVA showed that patients with SCD have reduced CVR (p < 0.001) and lower coherence (p < 0.001) in gray matter and white matter and reduced gain in gray matter only (p < 0.001). In terms of the speed of the response to CO2, tau (p < 0.001) and TFA phase (p < 0.001) were increased in SCD patients compared to healthy control subjects. These findings show that the cerebrovascular responsiveness to CO2 in patients with SCD is both decreased and slowed compared to healthy controls. [ABSTRACT FROM AUTHOR]