Creating a novel contrast between chronic infarcted and remote myocardium by altering the duration of small angle RAFF2 pulses

Background: Relaxation Along a Fictitious Field in the second rotating frame (RAFF2) with the orientation of the fictitious field at the a⁽²⁾ =45° has demonstrated to characterize fibrosis-related myocardial diseases [1]. Simulations have shown a significant increase in exchange-induced relaxation rate constants that correspond to the frequency side bands generated during periodic irradiation with RAFF2 when a⁽²⁾ is only a few degrees [2]. The frequency of the side bands can be tuned by altering the duration of the RAFF2 pulse. Therefore, tuning RAFF2 pulse to alter the sensitivity of RAFF2 measurement for specific chemical shifts and possibly to probe specific pathological changes.

Methods: First, the spin dynamics of two pool chemical exchange were simulated using Bloch-McConnell equations using RAFF2 pulses with a⁽²⁾ = 3, 5, 8, 10 and 15° degrees and the pulse durations with stretching factor (TL)=0.6-2.0. Second, the same pulses were used to image ex vivo hearts of C57BL (n=6) mice with 14 days old infarction at 9.4T. Due to variation in small a⁽²⁾ angle RAFF2 pulse duration, maximum number of pulses in pulse train varied from 4 to 32 and 2-D fast-spin echo readout was used. As a comparison, original RAFFn-45° (n=1-5), T_1r, T_2r, and T₂ were used to validate the findings.

Results: Relaxation times decrease monotonically when RAFF2 TL increases from 0.6 to 2.0 in both infarcted and remote areas (Figure 1). Higher relaxation times with lower TLs are associated with infarcted areas as compared to the remote of the myocardium (Figures 1,2). As TL increases, relaxation time constants in infarcted and remote areas become more similar and as TL continues to increase, relaxation time difference inverts between the infarcted and remote areas (Figures 1,2). Other MRI methods had higher relaxation times in infarct compared to remote areas (Table 1). Simulations showed that side bands are generated by the RAFF2 pulses with the small a⁽²⁾ angles due to the periodicity of irradiation, and these side bands shift to larger offset frequencies as the duration of RAFF2 pulse increases (Figure 3).

Conclusion: Two pool exchange simulations showed that with small a⁽²⁾ angles there is a difference in offset frequencies when the durations of the RAFF2 pulse are altered. By altering durations of RAFF2 pulses with the small a⁽²⁾ can create a novel contrast between infarcted and remote areas. Interestingly, as the durations of the RAFF2 pulses increased, the remote areas had longer relaxation time constants as compared to infarcted areas. This inversion of contrast can be potentially due to offset frequency of the side bands generated by the periodic irradiation of RAFF2; however, the effects of altering TL’s and effect of used power in refocusing cannot be also excluded. This strategy outlines a novel way to evaluate molecular dynamics in the infarcted heart and may reveal pathological structures in the infarcted heart.

Mean and standard deviation values of other relaxation time methods (TRAFFn are done with a(2) angle of 45) to compare the findings of small a(2) angle RAFF2 method.

Relaxation method	Infarcted (ms)	Remote (ms)
TRAFF1	55.6 ± 12.2	52.0 ± 11.5
TRAFF2	78.4 ± 16.4	73.6 ± 16.5
TRAFF3	111.8 ± 24.2	105.4 ± 23.7
TRAFF4	320.5 ± 51.2	304.5 ± 40.6
TRAFF5	435.4 ± 53.8	399.2 ± 48.4
CW T1p	45.2 ± 5.6	40.4 ± 5.5
T1p HS1	127.2 ± 14.1	116.0 ± 14.3
T1p HS4	79.2 ± 9.8	71.2 ± 10.2
T2p HS1	44.6 ± 5.5	41.2 ± 5.5
T2p HS4	50.2 ± 5.4	45.8 ± 6.4
T2	38.0 ± 4.3	36.6 ± 4.2

Figure 1. Average rotating frame relaxation times with different a(2) angles and the durations of the RAFF2 pulse.
Figure 2. Illustration of relaxation time maps from TL0.6, TL1.0 and TL2.0 (columns) in (2) angles of 5°, 8° and 10° (rows). Black line refers to infarcted area.
Figure 3. The results of the simulations show the offset resonance side bands of different durations of the RAFF2 pulse with specific a(2) angle. In the figure, there are RAFF2 with a(2) angle of 3° (A), 5° (B), 8° (C), 10° (D) and 15° (E).