SUPPLEMENTARY MATERIAL 2
An overview of Magnetization Transfer Imaging (MTI) studies in schizophrenia
No. (C1) / Study / Sample Overlap (No. in C1) / Approach / Scan / Tissue examined / Controls / Schizophrenia / Abnormalities reported in schizophreniaN / M/F / Age / N / M/F / Age / Subcategories
1 / Foong 20001 / 2 / ROI (4 lobes and CC) / 1.5 T / Whole Brain / 30 / 22/8 / 35.1 (25-49) / 25 / 19/6 / 37.3 (25-46) / DOI 14.3 (3-22); all medicated / Reduced MTR: Right and left temporal lobe. Effect of cognitive variables not tested
2 / Foong 20012 / 1 / VBA / 1.5 T / Whole Brain / 30 / 22/8 / 35.1 (25-49) / 25 / 19/6 / 37.3 (25-46) / DOI 14.3 (3-22); all medicated / Reduced MTR (all GM): inferior and middle frontal, inferior and middle temporal (both GM and WM), and superior occipital gyri. Effect of cognitive variables not tested
4 / Bagary 20023 / ROI: Thalamus only / 1.5 T / Anatomical ROI / 25 / 19/6 / 35.2 (24-49) / 25 / 19/6 / 37.2 (25-46) / DOI 14.3 years (range 3–22); all medicated / Thalamus only: No MTR abnormalities.Premorbid IQ showed no relationship with MTR measures.
5 / Bagary 20034 / 9 / VBA / 1.5 T / Whole Brain / 30 / 18/12 / (21-49) / 30 / 19/11 / 27.3 (18-47) / First episode; DOI 5.3(1-14) months; 5 unmedicated / Reduced MTR: Right medial PFC, left insula, left uncinate fasciculus. Effect of cognitive variables not tested
6 / Kiefer 20045 / ROI: Hippocampal formation / 1.5 T / Anatomical ROI / 14 / 9/5 / 31.0 (SD 6.5) / 14 / 9/5 / 31.4 (SD 10.8) / DOI 3.31 (3.7) years; All medicated / No MTR differences in Hippocampal ROI. Effect of cognitive variables not tested
7 / Kalus 20056 / ROI: Amygdala only / 1.5 T / Anatomical ROI / 14 / 9/5 / 31.37 (SD:6.0) / 14 / 9/5 / 27.93 (SD 6.4) / DOI 2.22(2.23) years; all medicated / No MTR differences in Amygdala ROI. Effect of cognitive variables not tested.
8 / Antosik-Biernacka 20067 / . / VBA / 3 T / Whole Brain / 23 / 13/10 / 33.9 (25-47) / 20 / 13/7 / 35.5 (23–45) / DOI 10.7 (5.8) years / Reduced MTR: Trend not reaching significance -
Left superior temporal gyrus, Right occipital cortex, and left periventricular WM. Effect of cognitive variables not tested
9 / Price 20068 / 5 / VBA (longitudinal) / 1.5 T / Whole Brain / 12 / 4/8 / 31.6 (26-50) / 16 / 12/4 / 26.3 (16–45) / First episode sample on inception / No longitudinal MTR/WMV changes. Effect of cognitive variables not tested
10 / Kubicki 20059 / VBA / 1.5 T / WM only / 26 / N/A / N/A / 21 / N/A / N/A / N/A / Reduced MTR and FA: Superior occipitofrontal fasciculus, right internal capsule, corpus callosum, fornix. Right posterior CB – reduced MTR, normal FA. FA of CB associated with lower WCST scores.
11 / Price 201010 / VBA / 1.5T / Whole Brain / 47 / 27/20 / 24.8 (16-37) / 48 / 33/15 / 26.2 (16–50) / First episode / Reduced MTR: Right entorhinal cortex, fusiform, dentate and superior frontal gyri and in left superior frontal and inferior/rostral cingulate gyri..Effect of cognitive variables not tested
12 / Mandl 201011 / ROIs: Genu and UF only / 1.5T / Reconstructed WM tracts / 40 / 29/11 / 28.0 (18-45) / 40 / 30/10 / 26.8 (20-41) / DOI 25.1(17.4); all medicated / Increased MTR: Right UF. No differences in FA or RD. Effect of cognitive variables not tested
13 / De Weijer 2011a12 / 14 / ROIs: Average fiber approach (UF, AF, CST, Cingulum) / 3 T / Reconstructed WM tracts / 40 / 23/19 / 38.4 (21-66) / 42 / 25/19 / 36.9 (18-61) / DOI 13.6(12.9)y; 6 unmedicated / Increased MTR: AF bilaterally
Lower FA: UF, CST and AF (no MD, AD differences)
Higher RD: UF,AF,CST, cingulum
Effect of cognitive variables not tested
14 / De Weijer 2011b13 / 13 / ROIs: Average fiber approach (AF, UF, CST, Cingulum) / 3 T / Reconstructed WM tracts / 31 / 14/22 / 41.39 (21-66) / 32 / 14/21 / 39.6 (18-61) / DOI 12.5 years (12.5); 5 unmedicated / Increased MTR: AF bilaterally (associated with lower FA, higher RD on the left)
Effect of cognitive variables not tested
15 / Mandl 201214 / ROIs: 12 WM tracts / 1.5 T / Reconstructed WM tracts / 23 / 14/9 / 22.81 (SD 3.1) / 16 / 13/3 / 23.37 (SD 3.5) / All unmedicated; DOI 1.85(2.14) years / Increased MTR and MD: Right UF and left AF
IQ showed no relationship with MTR measures
16 / Bohner 201215 / VBA (histograms) / 1.5 T / Whole Brain / 29 / 17/12 / 25.7 (SD 5.2) / 16 / 12/4 / 25.8 (SD 5.8) / First episode; 12 unmedicated (UHR samples also studied) / Reduced MTR: Bilateral frontal WM reduction in schizophrenia. Ultra high risk subjects showed MTR reduction in extended amygdala (stria terminalis). Effect of cognitive variables not tested
17 / Bachmann 201216 / VBA / 3 T / Whole Brain / 32 / 21/12 / 33.5 (SD10.1) / 32 / 21/12 / 33.1 (SD 8.6) / Chronic schizophrenia (mean no. of previous episodes = 3); all medicated / Reduced MTR: Right calcarine, lingual and fusiform and inferior temporal, hippocampal regions
Effect of cognitive variables not tested
DOI: Duration of Illness ROI: Region of Interest CC: Corpus Callosum SD: Standard deviation (presented where range is not available) MTR: Magnetisation Transfer Ratio WMV: White Matter Volume GM: Grey Matter FA: Fractional Anisotropy PFC: Prefrontal cortex CB: Cingulum bundle WCST: Wisconsin Card Sorting Test AF: Arcuate Fasciculus UF: Uncinate Fasciculus CST: Corticospinal tract RD: Radial diffusivity AD: Axial diffusivity VBA: Voxel Based Analysis N/A Information not available
REFERENCES
1. Foong J, Maier M, Barker GJ, Brocklehurst S, Miller DH, Ron MA. In vivo investigation of white matter pathology in schizophrenia with magnetisation transfer imaging. J Neurol Neurosurg Psychiatr 2000 Jan; 68: 70–4.
2. Foong J, Symms MR, Barker GJ, Maier M, Woermann FG, Miller DH et al. Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging. Brain 2001 May 1; 124: 882–92.
3. Bagary MS, Foong J, Maier M, duBoulay G, Barker GJ, Miller DH et al. A magnetization transfer analysis of the thalamus in schizophrenia. J Neuropsychiatry Clin Neurosci 2002; 14: 443–8.
4. Bagary MS, Symms MR, Barker GJ, Mutsatsa SH, Joyce EM, Ron MA. Gray and White Matter Brain Abnormalities in First-Episode Schizophrenia Inferred From Magnetization Transfer Imaging. Arch Gen Psychiatry 2003 Aug 1; 60: 779–88.
5. Kiefer C, Slotboom J, Buri C, Gralla J, Remonda L, Dierks T et al. Differentiating hippocampal subregions by means of quantitative magnetization transfer and relaxometry: preliminary results. Neuroimage 2004 Nov; 23: 1093–9.
6. Kalus P, Slotboom J, Gallinat J, Wiest R, Ozdoba C, Federspiel A et al. The amygdala in schizophrenia: a trimodal magnetic resonance imaging study. Neurosci Lett 2005 Mar 3; 375: 151–6.
7. Antosik-Biernacka A, Peuskens H, De Hert M, Peuskens J, Sunaert S, Van Hecke P et al. Magnetization transfer imaging in chronic schizophrenia. Med Sci Monit 2006 Apr; 12: MT17–21.
8. Price G, Cercignani M, Bagary MS, Barnes TRE, Barker GJ, Joyce EM et al. A volumetric MRI and magnetization transfer imaging follow-up study of patients with first-episode schizophrenia. Schizophr Res 2006 Oct; 87: 100–8.
9. Kubicki M, Park H, Westin CF, Nestor PG, Mulkern RV, Maier SE et al. DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. Neuroimage 2005 Jul 15; 26: 1109–18.
10. Price G, Cercignani M, Chu EM, Barnes TRE, Barker GJ, Joyce EM et al. Brain pathology in first-episode psychosis: magnetization transfer imaging provides additional information to MRI measurements of volume loss. Neuroimage 2010 Jan 1; 49: 185–92.
11. Mandl RCW, Schnack HG, Luigjes J, van den Heuvel MP, Cahn W, Kahn RS et al. Tract-based analysis of magnetization transfer ratio and diffusion tensor imaging of the frontal and frontotemporal connections in schizophrenia. Schizophr Bull 2010 Jul; 36: 778–87.
12. de Weijer AD, Neggers SFW, Diederen KMS, Mandl RCW, Kahn RS, Hulshoff Pol HE et al. Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals. Hum Brain Mapp [Internet] 2011 Nov 23 [cited 2012 Jul 29];Available from:
13. de Weijer AD, Mandl RCW, Diederen KMJ, Neggers SFW, Kahn RS, Hulshoff Pol HE et al. Microstructural alterations of the arcuate fasciculus in schizophrenia patients with frequent auditory verbal hallucinations. Schizophr Res 2011 Aug; 130: 68–77.
14. Mandl RCW, Rais M, van Baal GCM, van Haren NEM, Cahn W, Kahn RS et al. Altered white matter connectivity in never-medicated patients with schizophrenia. Human brain mapping [Internet] 2012 Mar 28 [cited 2012 Jul 29];Available from:
15. Bohner G, Milakara D, Witthaus H, Gallinat J, Scheel M, Juckel G et al. MTR abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls. Schizophr Res 2012 May; 137: 85–90.
16. Bachmann S, Haffer S, Beschoner P, Viviani R. Imputation techniques for the detection of microstructural changes in schizophrenia, with an application to magnetization transfer imaging. Schizophr Res 2011 Oct; 132: 91–6.
7T MRI of myelination in schizophrenia