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Metabolic imaging of in vivo myocardium
Journal of Cardiovascular Magnetic Resonance volume 17, Article number: P251 (2015)
The equilibrium cellular water efflux rate constant [kio; mean water lifetime inverse] from contrast agent [CA]-enhanced MRI measures on-going cellular Na+,K+-ATPase activity [turnover]. Good literature [4 different labs] agreement shows substantial kio decreases in myocardial ischemia, hypertension, or infarct regions (Table). The 3 methods used differ in extracellular ("outside") CAo level manipulation to change the MR shutter-speed relative to kio and the MR exchange condition reached: A) CAo steady-state, slow-exchange-regime; B) CAo titration, fast-exchange-regime [FXR]; and C) CAo wash-out, FXR. The independent intracellular volume fraction [ICV] - cell density•volume product and ≈ 1 - ECV [extracellular volume fraction] - also decreases in pathology. We hypothesize that kio mapping shows metabolic compromise most effectively. We report initial experience with tissue near a repaired ventricular septal defect [VSD].
We acquired serial 1.5T 1H2O T1-weighted data from a 27 yo male before and 3 times after a bolus IV 0.15 mmol/kg CA [Omniscan] injection. Quantitative Look-Locker T1 measurements [non-selective inversion, 21 recovery times] imaged an 8 mm slice with a mid-ventricular short axis location inferior to the VSD patch. Method C (CAo wash-out, FXR) determined kio and ICV values in six LV wall segments.
The Figure shows a post-CA T1-w image: the endo- and epicardial LV wall edges as bright orange and green, respectively [light orange circle, an LV ROI]. Segmental ICV and kio values are given (yellow). Segments S5 and S6 comprise the septum. The ICV values for segments S1 - S4 are reasonable for normal myocardium (Table). Thus, we have indicated (*) a control myocardial kio value [5 s-1, Table], since the CA wash-out data quantity [3 points] and quality from these normal myocardium segments yielded insufficient precision. Interestingly, the kio value is reduced [4.5 s-1] in segment S6, and dramatically so [1.7 s-1; 66%↓] in segment S5, immediately inferior to the VSD patch.
The kio biomarker is a sensitive measure of on-going myocardial metabolic activity. Our result suggests that tissue nearby a VSD patch can be, or become, metabolically compromised.
The ultimate goal is pixel-wise kio and ICV maps. [Here, nominal voxels are 2x2x8 mm3 = 32 μL.] For this, one needs data with good S/N and more than 3 wash-out points. Also, method C has systematic error absent in methods A and B, which cannot be used for humans. It assumes the CAo concentration equals that of CAp [in plasma] during wash-out. This is invalid for finite CA intravasation kinetics, which may be particularly slow in myocardial lesions due to common reduced vascularization. Possible kio and ICV underestimations can be corrected using Ktrans [the CA extravasation transfer constant] from the bolus tissue wash-in time-course to calculate the CA intravasation rate constant.
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Springer, C.S., Broberg, C.S. & Rooney, W.D. Metabolic imaging of in vivo myocardium. J Cardiovasc Magn Reson 17, P251 (2015). https://doi.org/10.1186/1532-429X-17-S1-P251
- Ventricular Septal Defect
- Normal Myocardium
- Extracellular Volume Fraction
- Efflux Rate Constant
- Nominal Voxels