Region-specific Neurochemical profile differences in juvenile rat model for ADHD and control strain: a 1H MRS study @ 11.7T
Alireza Abaei1, Francesca Rizzo2, Dinesh K Deelchand3, Anne Subgang1, Johannes T. Schneider4, Andrea G. Ludolph5, and Volker Rasche1,6

1Medical Faculty, Core Facility Small Animal MRI, Ulm University, Ulm, Germany, 2Institute of Anatomy and Cell Biology, University of Ulm, Ulm, Germany, 3University of Minnesota, Minneapolis, MN, United States, 4Bruker BioSpin MRI GmbH, Ettlingen, Germany, 5Department of Child and Adolescent Psychiatry, University of Ulm, Ulm, Germany, 6Department of Internal Medicine II, University Hospital Ulm, Ulm, Germany


Assessment and reliable quantification of brain metabolites is of great interest for diagnosis and monitoring of neurodegenerative psychiatric disorders. Challenging in this context is the required spectral fidelity demanding a combination of rapid data acquisition, optimal frequency and phase correction, and excellent shimming of the volume of interest. In this contribution, an optimized STEAM sequence was combined with image-based shimming and single-shot frequency and phase correction. The method was applied to assessment of the difference between the metabolic profile of spontaneous hypertensive rats and Wistar-Kyoto rats. Statistically significant differences could be quantified in the striatum and the prefrontal cortex.


Neurodevelopmental psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) occur during adolescence, in which the brain undergoes some major re-organization with regards to anatomy, neuronal morphology and connectivity, receptor expression, and neurotransmitter release. The spontaneously hypertensive rat (SHR) has been established as a valuable model of ADHD[1,2]. The goal of this study was to investigate differences in the metabolic profile of SHR and Wistar-Kyoto rat (WKY) during adolescence at postnatal day 42. An MR acquisition protocol optimized for 11.7T field-strength was combined with dedicated spectral post-processing algorithms to achieve MR spectra of so far unmet spectral fidelity.


In vivo 1H MR spectra were acquired from the striatum and prefrontal cortex of WKY (N = 7) and SHR rat (N = 6) at postnatal day (P) 42. Experiments were performed at 500 MHz on a 11.7 T horizontal superconducting magnet with 16 cm bore size (117/16 USR BioSpec, AVANCE III, ParaVision 6.01, Bruker BioSpin, Ettlingen, Germany) equipped with a 9 cm inner diameter self-shielded gradient coil insert (Bruker BioSpin, Ettlingen, Germany) capable of supplying up to 750 mTm−1 in 80 μs rise time. A 72 mm birdcage quadrature volume resonator (Bruker) was used for excitation and a receive-only rat brain surface coil array 2x2 (Bruker) was used for signal reception. Volume-of-interests (VOI) were planned based on T2-weighted multi-slice RARE images. Field homogeneity was adjusted individually for each investigated region using MAPSHIM. A short-echo-time STEAM spectroscopy sequence (TR/TE/TM: 5000/3.5/10 ms, 256 acquisitions) combined with VAPOR water suppression was used[3]. Spectra were acquired from 18.5µl (striatum) and 27.5 μL (prefrontal cortex) volumes. Single-shot data were frequency and phase corrected prior to summation in Matlab[4]. Unsuppressed water signal was used as an internal reference as well as for eddy current correction. LCModel analysis was performed in the chemical shift range of 0.5–4.2 ppm [5].

Results and Discussion

Representative water-suppressed in vivo proton MR spectra of the investigated rat brain regions clearly show the well-resolved resonances of numerous cerebral metabolites signals (Fig. 1), obtained with sufficiently consistent spectral quality. The average full width at half-maximum found by LCModel was 0.025 ± 0.003 ppm (12.5 ± 1.5 Hz) in the striatum and 0.028 ± 0.002 ppm (14 ± 1Hz) in the prefrontal cortex of rats. Corresponding SNR were 24.9 ± 2.5 and 37.7 ± 3.8. Average cramer rao lower bound (CRLB) for GABA, Glu and Gln were 5, 1 and 3 in the prefrontal cortex and 5, 5 and 2 in the striatum, proving the reliability of the quantification of the metabolites of the glutamatergic and GABAergic neurotransmission systems. The high spectral quality achieved over the entire chemical shift range (0.5–4.2 ppm) ensured reliable and reproducible quantification of each of the brain metabolites. Significant differences in myo-inositol (Ins) and taurine (Tau) between WKY and SHR rats were found for both regions. In addition to aforementioned metabolites, strain-differences in glutamine (Gln) and glutathione (GSH) level in prefrontal cortex and phosphocholine (PCh) and in total choline level in striatum were observed. Strain dependent changes of metabolites from two brain regions are shown in Fig. 2. In spite of the fact that scyllo-Ins and N-acetylaspartylglutamate (NAAG) signal were incorporated into the basis set of LCModel as a model component corresponding concentration was only possible to quantify in the striatum. This data of absolute metabolite concentration will serve as a reference for future MRS studies investigating the psychotherapeutic effect of neuroleptics on juvenile rat brain.


Optimized STEAM sequences in combination with advanced single-shot frequency and phase correction, and image-based shimming enables the quantification of brain metabolites with high spectral fidelity and reproducibility allowing for the assessment of even tiny differences between the metabolic profile of WYK and SHR rats.


No acknowledgement found.


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Fig. 1 In vivo 1H NMR spectra measured from the striatum and prefrontal cortex of WKY and SHR rat pups on postnatal day (P) 42. STEAM, TE = 3.5 ms, TR = 5 s, NT = 256. Insets: RARE images with the selected VOIs in striatum and prefrontal cortex.

Fig. 2 Comparison of neurochemical profiles of SHR rats relative to the control WKY rats. Metabolite concentrations were measured from striatum (Left) and prefrontal cortex (Right) on P42, WKY (n = 7) and SHR (n = 6). * p < 0.05, ** p < 0.01.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)