Creatine kinase imaging CKI for in vivo whole-brain mapping of creatine kinase reaction kinetics, 2025, Widmaier et al.

[SNT Gatchaman]

Creatine kinase imaging CKI for in vivo whole-brain mapping of creatine kinase reaction kinetics

Spoiler: Authors

Widmaier, Mark; Kaiser, Antonia; Pandurevic, Pontus; Lim, Song-I; Döring, André; Huang, Zhiwei; Wenz, Daniel; Xiao, Ying; Jiang, Yun; Lin, Yan; Xin, Lijing

The creatine kinase (CK) is a key enzyme involved in brain bioenergetics, playing an important role in brain function and the pathogenesis of neurological and psychiatric diseases and cancers. However, imaging its activity noninvasively in the human brain remains a significant challenge.

This study aims to advance 31P magnetic resonance fingerprinting for Creatine Kinase Imaging (CKI). The method was implemented and validated on a clinical 7 Tesla MRI scanner. CKI enables whole-brain mapping of CK forward rate constant, revealing regional differences. Furthermore, a functional CKI (fCKI) study demonstrated a CK activation map in response to visual stimulation, revealing an increase in CK forward rate constant in the visual cortex.

The novel imaging modalities, CKI and fCKI, have the potential to offer insights into brain bioenergetics both at rest and during activity, in both healthy and pathological conditions.

SIGNIFICANCE
Creatine kinase (CK) is a key enzyme in brain bioenergetics, with its activity altered in various neurological disorders. This study introduces a CK Imaging (CKI) method to map CK forward rate constants across the entire brain in vivo. Furthermore, functional CKI extends this approach by capturing CK activation during functional tasks, revealing increased CK activity in the visual cortex during visual stimulation. The introduced methods could offer insights into brain energetics under both healthy and pathological conditions.

Web | DOI | PDF | Proceedings of the National Academy of Sciences | Paywall

 

[SNT Gatchaman]

I'll leave out all the technical points which are heavy on MRI physics and acronyms and the technical barriers that needed to be overcome. Creatine Kinase Imaging as described here is a novel neuroimaging modality that I think can be added to the list of studies we'd like to see in ME/CFS. Summary quotes from the paper —

The brain’s energy requirements are substantial, accounting for roughly 20% of the body’s total energy usage. […] Understanding the dynamics of brain energetics is vital for the advancement of diagnostic and therapeutic strategies for various health conditions. One of the key enzymes in cellular energy metabolism is Creatine Kinase (CK), which catalyzes the reversible reaction to transfer high-energy phosphate between phosphocreatine (PCr) and triphosphate (ATP):

PCr + ADP + H⁺ ⇄ ATP + creatine.

It plays a key role in cellular energy buffering, regeneration, and transport, and has emerged as a promising biomarker with diverse clinical implications.

Recent findings suggest a link between mitochondrial dysfunction and psychiatric disorders, as evidenced by reduced CK turnover rates in schizophrenia (22%) , first episode bipolar disorder (14%), and first-episode psychosis (12%).

In a proof-of-concept application, CKI was applied dynamically during visual stimulation, providing the first-ever 3D CK activation clusters in the visual cortex. This CKI application introduces a novel functional imaging modality, functional Creatine Kinase Imaging (fCKI), which provides insights into the bioenergetic mechanisms underlying brain function.

The CKI is a user-friendly method with a push-button acquisition. The reconstruction and matching procedures are fully automated. The excellent robustness of the method, coupled with its ease of application, underscores the potential for its use in clinical studies.

In conclusion, CKI provides an imaging method for wholebrain kCK mapping. […] Applied along with a functional task, fCKI provides a new functional imaging modality. The kCK activation mapping allows access to information on brain bioenergetics underlying brain function. CKI and fCKI have the potential to enhance our understanding of brain function and neurological dysfunctions, including neurodegenerative and psychiatric disorders.

They note it could also be applied to non-brain tissue / organs so could be used to evaluate muscle also as a follow-on from 1H and 31P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID (2024) and Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise In A Patient With A Post-Viral Exhaustion/Fatigue Syndrome: A 31P Nuclear Magnetic Resonance Study (1984)