Thornhill Scientific Inc.

James Duffin

Olivia Sobczyk

Joseph A Fisher

David J Mikulis

Julien Poublanc

Ece Su Sayin

Michael Klein

Joseph Arnold Fisher

Daniel Michael Mandell

Marat Slessarev

Shoji Ito

Adrian P Crawley

Kevin Sam

Cathie Kessler

Anne Battisti-Charbonney

Kamil Uludag

Jacob B Schulman

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 SaOenables the conversion of magnetic signal to SaOthroughout blood-containing voxels throughout the brain.

Method and system of measuring brain oxygenation using deoxyhemoglobin contrast

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.

System and method for determining arterial input function based on susceptibility contrast in the choroid plexus

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.

Implementing a periodic deoxyhemoglobin signal

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.

Identifying the vascularity of cerebral tissue in subjects using deoxyhemoglobin contrast

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.

Testing for neurovascular uncoupling in multiple sclerosis using sequential gas delivery versus fixed inspired CO

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.

Imaging abnormalities in vascular response

A method of controlling a gas delivery apparatus including an apparatus controllable variable using an iterative algorithm to deliver a test gas (TG) for non-invasively determining a subject's pulmonary blood flow comprising iteratively generating and evaluating test values of a iterated variable based on an iterative algorithm in order output a test value of the iterated variable that meets a test criterion wherein iterative algorithm is characterized in that it defines a test mathematical relationship between the at least one apparatus controllable variable, the iterated variable and an end tidal concentration of test gas attained by setting the apparatus controllable variable, such that the iterative algorithm is determinative of whether iteration on the test value satisfies a test criterion or iteratively generates a progressively refined test value.

Non-invasive cardiac output determination

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: &#x2014;obtaining input of a series of logistically attainable PetX values for a series of respective breaths: &#x2014;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&#x2014;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.

Method and apparatus to attain and maintain target arterial blood gas concentrations using ramp sequences

A processor obtains input of a logistically attainable end tidal partial pressure of gas X (PetX[i]) for one or more respective breaths [i] and input of a prospective computation of an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX[i]for a respective breath [i] using inputs required to utilize a mass balance relationship, wherein one or more values required to control the amount of gas X in a volume of gas delivered to the subject is output from an expression of the mass balance relationship. The mass balance relationship is expressed in a form which takes into account (prospectively), for a respective breath [i], the amount of gas X in the capillaries surrounding the alveoli and the amount of gas X in the alveoli, optionally based on a model of the lung which accounts for those sub-volumes of gas in the lung which substantially affect the alveolar gas X concentration affecting mass transfer.

Apparatus to attain and maintain target end tidal partial pressure of a gas

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 PetCO, 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's vasoactive response corresponding to a sub-series of the at least one of a series of targeted increments or decrements in the subject's PetCO, the sub-series characterized in that the specific portion of the subject's vasoactive response is the portion sensitive to quantifying a reduction in cerebrovascular reactivity.

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Toronto, Canada

James Duffin