Abstract: The present specification discloses a method for measuring brain tissue oxygenation in a subject. The method comprises the following steps: measuring a magnetic signal in a reference voxel of the subject's brain while imposing a series of arterial oxygen saturation changes using sequential gas delivery; calculating a relationship between the magnetic signal and the arterial oxygen saturation in the reference voxel; measuring a magnetic signal in a target voxel; and calculating the hemoglobin saturation in the target voxel based on the established relationship between the magnetic signal and the SaO2 in the reference voxel. This calibration of magnetic signal for SaO2 enables the conversion of magnetic signal to SaO2 throughout blood-containing voxels throughout the brain.

Abstract: Deoxyhemoglobin contrast has been used to locate arteries based on the earlier blood oxygen-level dependent (BOLD) signal arrival time, higher BOLD signal strength, and shorter mean transit time. However, additional strategies of identifying arteries with oxygen modulation are required to improve the sensitivity and specificity of results. The present disclosure provides a method of distinguishing extravascular voxels from intravascular voxels based on the magnetic signal obtained from two hypoxic boluses having two different baselines. Intravascular voxels are responsive to changes in the baseline due to their high blood volume, while extravascular voxels are not affected by changes to the baseline. Amongst intravascular voxels, arteries can be distinguished from veins because the extraction fraction of the arterial blood is reduced during hypoxia, and therefore veins are less sensitive to changes in the baseline.

Abstract: The speed and range of the transition to low lung PO2 can be optimized such that it approaches the PO2 and timing profile of reoxygenation from a hypoxic profile. However, such hypoxic “spikes” are much more difficult to implement than re-oxygenation. A solution is to control the independent variables which contribute to hypoxia in the lung. These variables may be controlled in alone or in aggregate to minimize the time required to generate a target profile of transient lung hypoxia. In particular, a rapid decrease in [dOHb] can be implemented by breathing deeply, exhaling at least a portion of the functional residual capacity, lowering the PO2 at baseline, increasing the breathing rate, and increasing the PCO2 to shift the oxygen-hemoglobin dissociation curve to the right.

Abstract: A method of implementing changes in deoxyhemoglobin concentration, the method comprising: targeting a sequence of partial pressures of oxygen in arterial blood (PaCh) values in a subject using a sequential gas delivery device in a periodic input pattern; measuring a blood-oxygen level dependent (BOLD) signal in a voxel of the subject's brain using a magnetic resonance imaging device while targeting the sequence of values; comparing the pattern to the signal; and determining a vascular tissue characteristic (vessel type, vessel orientation, or pathological condition) for the voxel based on the comparison.

Abstract: Hypoxia-induced deoxy hemoglobin concentration ([dOHb]) may be used as a susceptibility contrast agent in subjects. While the maximal rate of generating blood [dOHb] are limited by constraints in pulmonary gas mixing, decreasing dOHb with reoxygenation of the lungs can be accomplished in one breath, resulting in a step reduction in arterial [dOHb] and thereby a step increase in cerebral BOLD signal recorded with MRI. The BOLD signal changes accompanying a step decrease in [dOHb] can be analyzed to calculate cerebral perfusion measures and compare their maps to those obtained using a bolus of a conventional contrast agent, gadolinium, and a conventional analysis requiring the identification of an arterial input function. The two methods provided comparable anatomically-distributed hemodynamic information.

Abstract: An apparatus and method for assessing vascular compliance in subjects with multiple sclerosis using sequential gas delivery is provided. The apparatus includes a gas delivery device and a processor. The processor controls the gas delivery device to deliver a first and second gas during a single inspiration. The first gas contains a mixture of oxygen and carbon dioxide necessary to target an end-tidal concentration of the two gases. The second gas includes a concentration of carbon dioxide equal to the target end-tidal concentration of carbon dioxide.

Abstract: Z maps combined with a standardized stimulus in the form of a targeted arterial partial pressures of carbon dioxide provide suprisingly enhanced images for the assessment of pathological CVR. For example, the z-map assessment of patients with known steno-occlusive diseases of the cervico-cerebral vasculature showed an enhanced resolution of the presence, localization, and severity of the pathological CVR. Z-map have been found to be useful to reduce the confounding effects of test-to-test, subject-to-subject, and platform-to-platform variability for comparison of CVR images showing the importance of combining this analysis with the standardized stimulus.

Abstract: Z maps combined with a standardized stimulus in the form of a targeted arterial partial pressures of carbon dioxide provide surprisingly enhanced images for the assessment of pathological CVR. For example, the z-map assessment of patients with known steno-occlusive diseases of the cervico-cerebral vasculature showed an enhanced resolution of the presence, localization, and severity of the pathological CVR. Z-map have been found to be useful to reduce the confounding effects of test-to-test, subject-to-subject, and platform-to-platform variability for comparison of CVR images showing the importance of combining this analysis with the standardized stimulus.

Abstract: Conventionally, the arterial input function is determined by administering a contrast agent and measuring the responsive magnetic signal in a reference voxel located in a large artery such as the middle cerebral artery. By instead measuring the signal in a voxel of the choroid plexus, a more accurate profile for the arterial input function may be obtained. The metabolic activity in the choroid plexus is negligible, which provides greater certainty for signal sampling.

Abstract: Deoxyhemoglobin in a subject may be modulated to act as a contrast agent for use in magnetic resonance imaging. Sequential gas delivery may be applied to adjust the level of deoxyhemoglobin in the subject. A suitable magnetic resonance imaging (MRI) pulse sequence that is sensitive to magnetic field inhomogeneities, such as a blood-oxygen-level dependent (BOLD) sequence, may be used to detect deoxyhemoglobin as a contrast agent.

Abstract: Alveolar dead space of a subject is determined by measuring an end tidal partial pressure of carbon dioxide during a sequence of normal breaths of the subject and, during a sequence of deep breaths by the subject, delivering a first volume of a first gas to the subject over a first portion of each inspiration by the subject. The first volume is less than or equal to an expected alveolar volume of the subject when the subject is breathing normally. A second volume of a second gas is delivered to the subject over a second portion of each inspiration. The second gas includes a neutral gas. An end tidal partial pressure of carbon dioxide is measured during the sequence of deep breaths. The alveolar dead space is computed using the end tidal partial pressures of carbon dioxide measured during the sequence of normal breaths and the sequence of deep breaths.

Abstract: An apparatus and method for controlling the end tidal partial pressure of a gas X in a subject's lung, and to the use of such an apparatus and method for research, diagnostic and therapeutic purposes, wherein the method consists of: -obtaining input of a series of logistically attainable PetX values for a series of respective breaths: -determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX for each of said respective breaths; and controlling a gas delivery device to deliver the amount of gas in a volume of gas delivered to the subject in each of said respective breaths to target the respective PetX for that breath.

Abstract: An apparatus and method for controlling the end tidal partial pressure of a gas X in a subject's lung, and to the use of such an apparatus and method for research, diagnostic and therapeutic purposes, wherein the method consists of: —obtaining input of a series of logistically attainable PetX values for a series of respective breaths: —determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX for each of said respective breaths: and—controlling a gas delivery device to deliver the amount of gas in a volume of gas delivered to the subject in each of said respective breaths to target the respective PetX for that breath.

Abstract: An apparatus and method for assessing vascular compliance in subjects with multiple sclerosis using sequential gas delivery is provided. The apparatus includes a gas delivery device and a processor. The processor controls the gas delivery device to deliver a first and second gas during a single inspiration. The first gas contains a mixture of oxygen and carbon dioxide necessary to target an end-tidal concentration of the two gases. The second gas includes a concentration of carbon dioxide equal to the target end-tidal concentration of carbon dioxide.

Abstract: A system for detecting an abnormality in a subject's cerebrovascular response to a vasoactive stimulus in at least one region of interest (ROI) of the subject's brain The system comprises a system for generating the vasoactive stimulus (SVS), the SVS including a gas delivery device and a control system operable to deliver controlled amounts of carbon dioxide effective to attain at least one of a series of targeted increments or decrements in the subject's PetCO2, for a series of respective intervals; an imaging system comprising an MRI scanner for generating response signals corresponding to the subject's vasoactive response to the vasoactive stimulus; and a computer for analyzing the response signals, the computer including program code for computing at least one value representing a quantitative measure of the subject's cerebrovascular reactivity for the ROI, wherein the at least one value is obtained for a specific portion of the subject's vasoactive response in the ROI, the specific portion of the subject

Abstract: An apparatus and method for controlling the end tidal partial pressure of a gas X in a subject's lung, and to the use of such an apparatus and method for research, diagnostic and therapeutic purposes, wherein the method consists of: obtaining input of a series of logistically attainable PetX values for a series of respective breaths: determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX for each of said respective breaths: and controlling a gas delivery device to deliver the amount of gas in a volume of gas delivered to the subject in each of said respective breaths to target the respective PetX for that breath.

Abstract: Z maps combined with a standardized stimulus in the form of a targeted arterial partial pressures of carbon dioxide provide suprisingly enhanced images for the assessment of pathological CVR. For example, the z-map assessment of patients with known steno-occlusive diseases of the cervico-cerebral vasculature showed an enhanced resolution of the presence, localization, and severity of the pathological CVR. Z-map have been found to be useful to reduce the confounding effects of test-to-test, subject-to-subject, and platform-to-platform variability for comparison of CVR images showing the importance of combining this analysis with the standardized stimulus.

Abstract: An algorithm including program code for analyzing a specific portion of the vasoactive response to the vasoactive stimulus corresponding to a to sub-range of increments and/or decrements of stimuli within the full range of the vasoactive stimulus, the sub-range characterized in that is more sensitive to identifying reductions in vascular reactivity in the ROI.

Abstract: An apparatus and method for controlling the end tidal partial pressure of a gas X in a subject's lung, and to the use of such an apparatus and method for research, diagnostic and therapeutic purposes, wherein the method consists of: obtaining input of a series of logistically attainable PetX values for a series of respective breaths: determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX for each of said respective breaths: and controlling a gas delivery device to deliver the amount of gas in a volume of gas delivered to the subject in each of said respective breaths to target the respective PetX for that breath.