Ichise's Multilinear Reference Tissue Model 2 (MRTM2)

MRTM can be turned into a more robust method called MRTM2 for pixel-wise applications with the same two-step approach applied in SRTM2:

1. Calculate the clearance rate k₂' of the reference TAC by MRTM or SRTM with VOI data which has a limited level of noise. To reduce the variability of the k₂' estimate, the result from different high-BP VOIs can be averaged.
2. Fix k₂': Use the estimated k₂' value for the pixel-wise MRTM calculations, reducing the number of fitted parameters from 3 to 2.

If k'₂ is fixed, the equation of MRTM reduces to

with only two regression coefficients V/(V'b) and 1/b for T > t*. BP is then calculated from the ratio of the two regression coefficients as

Implementation Notes

After switching to the Ichise NonInvasive MRTM2 in PKIN a suitable reference region must be selected. k₂' is an input parameter which must be manually edited, or estimated by using first the MRTM or SRTM model. MRTM2 allows to fit a multilinear regression within a range starting at the parameters Start Lin. The results are two regression coefficients, and the derived binding potential BP.

There is also an error criterion Max Err. to fit Start Lin. For instance, if Max Err. is set to 10% and the fit box of Start Lin. is checked, the model searches the earliest sample so that the deviation between the regression and all measurements is less than 10%. Samples earlier than the Start Lin. time are disregarded for regression and thus painted in gray.

Note: The k₂' resulting from the SRTM or MRTM method is a suitable estimate. Therefore, when switching in PKIN from the SRTM or MRTM model to MRTM2, k₂' is automatically copied , as long as Model conversion in the Configuration menu is enabled. See also.

Abstract [33]

"We developed and applied two new linearized reference tissue models for parametric images of binding potential (BP) and relative delivery (R₁₎ for [11C]DASB PET imaging of 5-HT transporters in human brain. The original multilinear reference tissue model (MRTMO) was modified (MRTM) and used to estimate a clearance rate (k₂' ) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM₂) by fixing k₂' . The resulting BP and R₁ estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM₂, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k₂' estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTMO from 12-70% to 1-4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of 2-3 over MRTM or SRTM. MRTM₂, SRTM₂ and 1TKA had R₁ bias < 0.3% and variability at least a factor of 2 lower than MRTM or SRTM. MRTM₂ allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM₂ should be a useful method for human [11C]DASB PET studies."