University of Pittsburgh

4D Oxy-Wavelet MRI for Monitoring Mitochondrial Function

University of Pittsburgh and Cedars-Sinai Medical Center scientists have developed a novel MRI (magnetic resonance imaging) method, 4D Oxy-wavelet MRI, to monitor mitochondrial function in live tissue (e.g., a beating heart or a live brain). This non-invasive approach can simultaneously monitor oxygen homeostasis and structural properties of organs and could aid the detection of mitochondrial disease linked to numerous health conditions

(Above is an in vivo 4D Oxy-wavelet MRI scan of the long axis (A) and short axis (B) of a mouse heart.)

Description

Mitochondrial dysfunction (MD) is a key element of inborn and acquired pathologies including neurogenerative disease, epileptic encephalopathy and some heart diseases, especially heart failure with preserved ejection fraction. Recently MD has been linked to acquired epilepsy after traumatic brain injury (TBI). There exists a great clinical need for a non-invasive technique to determine mitochondrial function for diagnostic purposes and to assess the efficacy of any treatment plan. 4D Oxy-wavelet MRI can probe mitochondrial function using blood-oxygen-level-dependent (BOLD) contrast in response to oscillating hypoxia challenges, providing a novel non-invasive approach to diagnosis of MD.

Applications

• Fetal medicine
• Mitochondrial disease
• Acquired epilepsy

Advantages

While mitochondrial dysfunction can be assessed using lumbar puncture or from therapeutically removed brain samples from TBI patients, both techniques are highly invasive and not always suitable in fetal medicine. MD impacts on the sensing and maintenance of cellular oxygenation levels. 4D Oxy-Wavelet MRI utilizes this as a biomarker of MD. BOLD contrast has previously been used for fMRI for other applications and is useful to observe deoxy-hemoglobin and regional hemodynamic changes in the brain. This novel 4D MRI technique can non-invasively observe changes in BOLD signals with high spatial and temporal resolution and high signal-to-noise ratios, without motion artefacts. Oxygen homeostasis can be assessed during hypoxia, with abnormal results indicating MD. Understanding the regions of the brain impacted by MD could allow clinicians to diagnose MD and monitor improvements from treatment.

Invention Readiness

In vivo studies in mice demonstrated 4D Oxy-wavelet MRI could determine neurodevelopmental, congenital heart disease, peri-conceptional alcohol exposure and fetal irradiation injury in utero. Other examples confirmed the novel MRI technique could identify MD associated with Alzheimerメs disease and doxorubicin-induced MD before cardiomyopathy was observed.

IP Status

https://patents.google.com/patent/US20240353513A1