Quantification of Tryptophan and NAD⁺ Proton Magnetization Exchange With Water Using Downfield ¹H MRS in the Human...

The purpose of this study was to investigate the effect of magnetization exchange on the measurement of tryptophan and NAD⁺ T₁ relaxation times and to determine the magnetization exchange rates with a two-spin system model using downfield ¹H MRS spectroscopy at 7 T in human brain.

We collected downfield ¹H MRS spectra in the human brain of eight healthy volunteers using a spectrally selective single-slice sequence (excitation window: 9.7 ± 2 ppm) at 7 T. Alternating selective and broadband saturation recovery experiments were performed to probe magnetization transfer-dependent changes in T₁ recovery. The apparent T₁ was modeled independently for each experiment for the tryptophan resonance at 10.1 ppm and for the NAD⁺ resonances at 9.3, 9.1, and 8.9 ppm. The magnetization exchange rate was modeled explicitly using a two-spin model to fit both experiments simultaneously.

The apparent T₁ relaxation times measured from broadband saturation recovery experiments were significantly longer for each resonance compared to those measured from selective saturation (p < 0.001). The ratio of broadband to selective T₁ was significantly larger for tryptophan than NAD⁺ (TRP: 19 ± 6 vs. NAD⁺: 9 ± 3; p < 0.01). Using the two-spin model, we modeled the T₁ of each resonance (ms): T_1,TRP = 622.3 ± 405.5; T_1,NAD,H2 = 924.9 ± 233.7; T_1,NAD,H6 = 1800.0 ± 985.5; T_1,NAD,H4 = 2057.3 ± 573.5. The chemical exchange rate of tryptophan was 12.3 ± 3.1 Hz; the cross-relaxation rates of NAD⁺ were (Hz): σ_NAD,H2 = 5.7 ± 1.6, σ_NAD,H6 = 3.3 ± 0.8, and σ_NAD,H4 = 3.0 ± 1.5. The tryptophan exchange rate was significantly faster than the rates for NAD⁺ (p < 0.001).

Tryptophan chemical exchange and NAD⁺ cross-relaxation with water can be quantified in vivo in human brain at 7 T using downfield spectroscopy.