Real-time measurement of diffusion exchange rate in biological tissue

Diffusion exchange spectroscopy (DEXSY) provides a means to isolate the signal attenuation associated with exchange from other sources of signal loss. With the total diffusion weighting b₁+b₂=b_s held constant, DEXSY signals acquired with b₁=0 or b₂=0 have no exchange weighting, while a DEXSY signal acquired with b₁=b₂ has maximal exchange weighting. The exchange rate can be estimated by fitting a diffusion exchange model to signals acquired with variable mixing times. Conventionally, acquired signals are normalized by a signal with b₁=0 and b₂=0 to remove the decay due to spin-lattice relaxation. Instead, division by a signal with equal b_s but b₁=0 or b₂=0 reduces spin-lattice relaxation weighting of the apparent exchange rate (AXR). Furthermore, apparent diffusion-weighted R₁ relaxation rates can be estimated from non-exchange-weighted DEXSY signals. Estimated R₁ values are utilized to remove signal decay due to spin-lattice relaxation from exchange-weighted signals, permitting a more precise estimate of AXR with less data. Data reduction methods are proposed and tested with regards to statistical accuracy and precision of AXR estimates on simulated and experimental data. Simulations show that the methods are capable of accurately measuring the ground-truth exchange rate. The methods remain accurate even when the assumption that DEXSY signals attenuate with b is violated, as occurs for restricted diffusion. Experimental data was collected from fixed neonatal mouse spinal cord samples at 25 and 7°C using the strong static magnetic field gradient produced by a single-sided permanent magnet (i.e., an NMR MOUSE). The most rapid method for exchange measurements requires only five data points (an 80 s experiment as implemented) and achieves a similar level of accuracy and precision to the baseline method using 44 data points. This represents a significant improvement in acquisition speed, overcoming a barrier which has limited the use of DEXSY on living specimen.