APT-Weighted MRI of Cancer & Ischemia
Hye-Young Heo1,2

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

Synopsis

Amide proton transfer-weighted (APTw) imaging, a variant of the CEST-based molecular MRI technique, is based on the chemical exchange between free bulk water protons and the amide protons (-NH) of mobile proteins and peptides. Theoretically, the APTw-MRI signal relies mainly on the mobile amide proton concentration and amide proton exchange rate which are related to tissue pH. Therefore, APTw-MRI has the potential to detect brain tumors (where many proteins are overexpressed) and ischemic strokes (where pH drop). Early pre-clinical and clinical data suggest that APTw imaging has unique features by which to detect and characterize brain tumors and strokes.

Highlights

APTw-MRI has great potential clinical utility for 1) identification of brain tumors from peritumoral edema and normal tissue, differentiation between high-grade from low-grade tumors, and differentiation treatment-related damage from tumor recurrence and 2) identification of ischemic acidosis penumbra and separation of ischemic stroke lesion from intracerebral hemorrhage.

Target Audience

Basic scientists and clinical scientists who are interested in APTw-MRI for pre-clinical and clinical applications.

Outcome/Objectives

Upon completion of this course, attendees should be able to 1) have a better basic understanding of APTw-MRI method, 2) update the most reported imaging findings as potential clinical applications, and 3) be made aware of methodological challenges, and current and possible future solutions.

Purpose

The presentation will provide detailed description of APTw-MRI technology and introduce its clinical applications.

APT-weighted MRI of cancer

Recent research in animals [1-3] and patients [4-11] with brain tumors has shown that APTw-MRI has the potential to enhance the noninvasive identification of brain tumors from peritumoral edema or normal tissue, to differentiate high-grade from low-grade tumors, to separate high- from low-grade tumors that do not show Gd enhancement, or to differentiate treatment-related damage from tumor recurrence. Therefore, APTw-MRI has high potential impact and add important value to the standard clinical MRI sequences in brain cancer diagnosis and therapy.

APT-weighted MRI of ischemia

pH-sensitive APTw imaging has shown promise in detecting ischemic tissue acidosis following impaired aerobic metabolism in animal models [12-17] and human stroke patients [18-21]. The region of pH abnormality, smaller than that of a perfusion abnormality and larger than that of a diffusion abnormality, is associated with the size of the final infarcted are without reperfusion. Thus, APTw-MRI based pH imaging may separate the perfusion/diffusion mismatch into an acidosis-based penumbra and a zone of benign oligemia that can recover spontaneously. Although definitive evidence is still lacking, this technique may be useful to help guide thrombolytic and/or neuroprotective therapies for acute stroke patients at various therapeutic windows.

Conclusion

MTRasym(3.5ppm)-based APT images are not clean in terms of just one component [22-31]. For that reason, we call them APT-weighted images. Importantly, based on numerous previous studies, this APT-weighted contrast has proven to be very accurate for the characteristic of high-grade tumors, making APTw-MRI a powerful and specific clinical indicator of presence of new or recurrent tumors [4-11], while several presumably cleaner contrasts are still in evaluation. Furthermore, we expect to have a clearer marker that can better be used for the diagnosis and prognosis of stroke patients.

Acknowledgements

I would like to thank Jinyuan Zhou and Peter van Zijl for insightful discussions contributing to this syllabus and my colleagues from the Johns Hopkins group for feedback during the preparation of this syllabus.

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Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)