Table 4.
Diagnostic accuracy of quantitative structural MR-based techniques including DWI, MTI, iron-sensitive sequences and NMI for the diagnosis of APD
| References | Cohort size | Magnetic field | Main results | Discriminator | Accuracy, % |
|---|---|---|---|---|---|
| Diffusion imaginga | |||||
| Schocke et al. (2002) | MSA-P 10/PD 11/HC 7 | 1.5 T | ↑ Putaminal diffusivity values in MSA-P compared to PD and HC No significant group differences of diffusivity values in the other ROIs. Significant correlation between UPDRS III and putaminal diffusivity values |
Putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. PD and HC) |
| Seppi et al. (2003)b | MSA-P 12/PD 13/PSP 10 | 1.5 T | ↑ Diffusivity values in putamen, globus pallidus, and caudate nucleus in PSP compared to PD No differences of diffusivity values of the different ROIs between PSP and MSA-P |
Putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. PD) Se 90 (PSP) Sp 100 (vs. PD) |
| Seppi et al. (2004)c | MSA-P 15/PD 17/HC 10 | 1.5 T | ↓ S/FC ratios and higher striatal diffusivity values in MSA-P compared to both PD and HC No significant differences in S/FC ratios and striatal diffusivity values between PD and HC Higher overall predictive accuracy of striatal diffusivity values (97%) compared to IBZM S/FC ratio (75%) |
Striatal diffusivity | Se 93 (MSA-P) Sp 100 (vs. PD and HC) |
| Schocke et al. (2004) | MSA-P 11/PD 17/HC 10 | 1.5 T | ↑ Putaminal and pallidal diffusivity values in MSA-P compared to both PD and HC Complete discrimination between MSA-P vs. PD and HC with putaminal diffusivity values in y- and z- direction Significant correlation between UPDRS III and putaminal diffusivity values |
Putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. PD and HC) |
| Shiga et al. (2005) | MSA 11 (8 MSA-C, 3 MSA-C)/HC 10 | 1.5 T | ↓ FA values in MCP, basis pontis and internal capsule Significant negative correlation of MCP FA values with ataxia scores |
FA in MCP | Se 100 (MSA-P and MSA-C) Sp 100 (vs. HC) |
| Seppi et al. (2006a) | MSA-P 15/PD 20/HC 11 | 1.5 T | ↑ Diffusivity values in the entire, anterior, and posterior putamen in MSA-P compared to PD and HC ↑ Diffusivity values in the posterior compared to the anterior putamen in MSA-P No significant differences between posterior and anterior putamen in PD and HC |
Putaminal diffusivity | Se 93 (MSA-P) Sp 100 (vs. PD and HC) |
| Seppi et al. (2006b) | MSA-P 15/PD 20/HC 11 | 1.5 T | ↑ Diffusivity values in the entire, anterior, and posterior putamen in MSA-P compared to PD and HC ↑ Diffusivity values in the posterior compared to the anterior putamen in MSA-P No significant differences between posterior and anterior putamen in PD and HC |
Posterior putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. PD and HC) |
| Nicoletti et al. (2006b) | MSA-P 16/PD 16/PSP 16/HC 15 | 1.5 T | ↑ Putaminal diffusivity values in MSA-P compared to PD and HC ↑ MCP diffusivity values in MSA-P compared to PD, HC and PSP |
MCP diffusivity | Se 100 (MSA-P) Sp 100 (vs. all groups) |
| Putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. PD and HC), 81 (vs. PSP) |
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| Kollensperger et al. (2007) | MSA-P 9/PD 9/HC 16 | 1.5 T | ↑ Putaminal diffusivity values in MSA-P compared to PD and HC No significant differences of blood pressure response to passive tilt between PD and MSA-P DWI was superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of MSA-P vs. the other groups |
Putaminal diffusivity | Se 100 (MSA-P) Sp 100 (vs. all groups) |
| Paviour et al. (2007) | MSA-P 11/PD 12/PSP 20/HC 7 | 1.5 T | ↑ Diffusivity values in the MCP and rostral pons in MSA-P compared to PSP and PD Significant correlation between diffusivity values in rostral pons and H&Y in MSA-P Significant correlation between globus pallidum diffusivity values and H&Y and UPDRS II and III |
MCP diffusivity | Se 91 (MSA-P) Sp 82 (vs. all groups), 84 (vs. PSP) |
| Ito et al. (2007) | MSA 20 (MSA-P 10, MSA-C 10)/PD 21/HC 20 | 3.0 T | ↑ Diffusivity values and significant lower FA values in the pons, cerebellum, and putamen in MSA compared to PD and HC All patients that had both significant low FA and high diffusivity values in each of the three regions were MSA-P cases, and those that had both normal FA and diffusivity values in the pons were all PD cases |
Diffusivity pons | Se 70 (MSA-P) Sp 70 (vs. PD) |
| Diffusivity cerebellum | 60 (MSA-P) Sp 88 (vs. PD) |
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| Diffusivity putamen | 70 (MSA-P) Sp 64 (vs. PD) |
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| FA pons | 70 (MSA-P) Sp 100 (vs. PD) |
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| FA cerebellum | 70 (MSA-P) Sp 64 (vs. PD) |
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| FA putamen | 70 (MSA-P) Sp 88 (vs. PD) |
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| Both low FA and high Diffusivity values in any of the three areas |
90 (MSA-P) Sp 100 (vs. PD) |
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| Nicoletti et al. (2008) | MSA-P 15/PD 16/PSP 28/HC 15 | 1.5 T | ↑ SCP diffusivity values in PSP compared to MSA-P, PD, and HC Assessment of diffusivity values in the SCP was not possible in two patients due to methodological reasons |
SCP diffusivity | Se 100 (PSP) Sp 100 (vs. PD and HC) Se 97 (PSP) 93 (vs. MSA-P) |
| Rizzo et al. (2008) | PSP-RS 10/CBS 7/PD 13/HC 9 | 1.5 T | ↑ Diffusivity in putamen and SCP in PSP-RS vs. PD ↑ Diffusivity in putamen in CBS vs. PD ↑ Hemispheric MD in CBS vs. PD and PSP-RS ↓ Hemispheric symmetry ratio in CBS vs. PD and PSP-RS |
Putaminal diffusivity | Se 80 (PSP-RS) Sp 77 (vs. PD) Se 86 (CBS) Sp 92 (vs. PD) |
| SCP diffusivity | Se 90 (PSP-RS) Sp 85 (vs. PD) |
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| Hemispheric MD | Se 86 (CBS vs. PD) Sp 85 (CBS vs. PD) Se 100 (CBS vs. PSP-RS) Sp 90 (CBS vs. PSP-RS) |
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| Hemispheric symmetry ratio | Se 100 (CBS vs. PD and PSP-RS) Sp 100 (CBS vs. PD and PSP-RS) |
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| Chung et al. (2009) | PD 12/MSA-P 10/HC 10 | 1.5 T | ↑ Diffusivity in dorsal putamen and MCP in MSA-P vs. PD and HC | Diffusivity dorsal putamen | Se 67 (MSA-P) Sp 80 (vs. PD) |
| Diffusivity MCP | Se 92 (MSA-P) Sp 100 (vs. PD) |
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| Boelmans et al. (2010) | CBS 14/PD 14/HC 14 | 1.5 T | ↑ MD in corpus callosum in CBS vs. PD and HC ↓ FA in middle-dorsal (sensory) corpus callosum in CBS vs. PD and HC No differences between PD and HC |
MD in corpus callosum | Se 79 (CBS) Sp 79 (vs. PD) |
| MD in middle-dorsal corpus callosum | Se 86 (CBS) Sp 71 (CBS vs. PD) |
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| Wang et al. (2012a, b) | MSA 31 (MSA-P 12, MSA-C 19)/PD 20/HC 20 | 1.5 T | ↑ Diffusivity values in the MCP and cerebellum in MSA-P and MSA-C compared to HC ↓ FA values in the pyramidal tract, MCP, and white matter of the cerebellum in MSA-C and MSA-P compared to HC No significant diffusivity changes in PD compared to HC |
Diffusivitycerebellum | Se 95 (MSA-C), 75 (MSA-P) Sp 85 (vs. PD and HC) |
| FA cerebellum | Se 95 (MSA-C), 83 (MSA-P) Sp 80 (vs. PD and HC) |
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| Diffusivity cerebellum | Se 58 (MSA-C) Sp 100 (vs. PD and HC) |
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| Diffusivity basal ganglia | Se 52 (MSA) Sp 90 (vs. HC) |
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| Nicoletti et al. (2013) | 9 MSA-P/7 MSA-C/17 PSP-RS/10 PD/10 HC | 1.5 T | ↑ Median MD values in whole infratentorial compartment, brainstem and cerebellum in MSA-P and MSA-C vs. other groups ↑ MD values in the cerebellar vermis in MSA-C vs. MSA-P ↑ MD in the vermis in PSP vs. PD and HC |
MD in whole infratentorial compartment | Se 100 (MSA-C and MSA-P) Sp 100 (MSA-C and MSA-P vs. other groups) |
| MD in the vermis | Se 100 (PSP vs. HC and PD) Sp 100 (PSP vs. HC and PD) |
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| Umemura et al. (2013) | MSA 20/PD 118 | 1.5 T | ↑ Putaminal diffusivity in MSA-P vs. PD | Putaminal diffusivity | Se 85 (MSA-P) Sp 89 (vs. PD) |
| Surova et al. (2013) | PD 10/MSA-P 12/PSP 16/HC 16 | 3.0 T | ↑ MD, RD, and ↓ FA in corpus callosum in PSP vs. PD and HC Increased apparent area coefficient in frontal and parietal cingulum and ↑ MD in corticospinal tract in PSP vs. PD ↑ RD in MSA-P vs. PD |
Apparent area coefficient in frontal and parietal cingulum | Se 87 (PSP) Sp 80 (PSP vs. PD) AUC = 0.88 |
| MD in corticospinal tract | Se 94 (PSP) 80 (PSP vs. PD) AUC = 0.85 |
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| MD in corpus callosum | Se 81 (PSP) 80 (PSP vs. PD) AUC = 0.85 |
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| Prodoehl et al. (2013) | PD 15/MSA 14/PSP 12/ ET 14/HC 17 |
3.0 T | Multi-target imaging approach focused on the basal ganglia and cerebellum accurately classifies control subjects and patients with PD, MSA-P, PSP, and ET SN, putamen, caudate, and MCP were the most frequently selected brain regions across classifications |
Model using DTI measures from the putamen, pallidum, SN, red nucleus, and MCP | Se 92 (HC) Sp 91 (HC vs. PD, MSA, PSP) AUC = 0.99 |
| Model using DTI measures from the putamen, SN, and dentate nucleus | Se 90 (PD) Sp 100 (PD vs. MSA, PSP) AUC = 0.99 |
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| Model using DTI measures from the SN and MCP | Se 94 (PD) Sp 100 (PD vs. MSA) AUC = 0.99 |
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| Model using DTI measures from the putamen and SN | Se 87 (PD) Sp 100 (PD vs. PSP) AUC = 0.96 |
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| Model using DTI measures from caudate and MCP | Se 90 (MSA) 100 (MSA vs. PSP) AUC = 0.97 |
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| Baudrexel et al. (2014) | PD 13/PSP 8/MSA-P 11/HC 6 | 3.0 T | ↑ MD in posterior putamen in MSA-P vs. PD, PSP, and HC ↑ MD in anterior putamen in MSA-P vs. PD |
MD posterior putamen | Se 73 (MSA-P) Sp 100 (vs. other groups) AUC = 0.89 |
| Meijer et al. (2015a, b) | Clinically uncertain parkinsonism 60 (of which n = 30 developed PD and n = 19 patients developed atypical parkinsonism: 12 MSA-P/3 PSP/3 DLB/1 CBS) | 3.0 T | DTI did not significantly improve the diagnostic accuracy of conventional brain MRI to differentiate the group of AP from PD The diagnostic accuracy to identify MSA-P was slightly increased by combining conventional MRI with DTI ↑ MD of the centrum semiovale, body corpus callosum, putamen, external capsule, midbrain, superior cerebellum, and SCP was found in clinically uncertain parkinsonism that developed AP ↑ MD of the putamen in clinically uncertain parkinsonism that developed MSA-P vs. PD ↑ MD in the midbrain and SCP in clinically uncertain parkinsonism that developed PSP vs. PD and MSA-P |
MD in putamen, midbrain, and SCP | AUC = 0.75 (atypical parkinsonism vs. PD) |
| Combination of conventional brain MRI and DTI | AUC = 0.83 (atypical parkinsonism vs. PD) AUC = 0.85 (MSA vs. other group) |
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| Surova et al. (2015) | PSP 27/MSA-P 11/PD 10/HC 21 | 3.0 T | ↑ MD in thalamus, ventral anterior, and ventral posterior thalamic nuclei and midbrain in PSP vs. MSA-P, PD, and HC ↑ MD in pons and putamen in MSA-P vs. PD and HC ↑ MD and decreased FA of bilateral DRTT in PSP vs. MSA-P, PD, and HC ↓ Thalamus, putamen, and pallidus volumes and midbrain area in PSP vs. MSA-P, PD, and HC in both cohorts ↓ Putamen and pallidus volumes in MSA-P vs. PD and HC |
MD of the thalamus | Se 81 (PSP) Sp 77 (vs. PD and MSA-P) AUC = 0.81 (vs. PD and MSA-P |
| MD right DRTT | Se 92 (PSP) Sp 81 (vs. PD and MSA-P), AUC = 0.94 (vs. PD and MSA-P |
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| MD midbrain | Se 81 (PSP) Sp 81 (vs. PD and MSA-P) AUC = 0.90 (vs. PD and MSA-P |
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| Planetta et al. (2016) | PD 18/MSA 18/PSP 18/HC 18 | 3.0 T | ↑ FW in the anterior and posterior SN of PD, MSA, and PSP vs. HC ↑ free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of MSA, and in all regions examined for PSP ↑ FW-corrected FA values for MSA in the putamen and caudate compared with PD and HC ↑ FW-corrected FA values for PSP in the putamen, caudate, thalamus, and vermis, and decreased in the SCP and corpus callosum compared with PD and HC |
Model including FW in posterior SN and FA in SCP | Se 94 (HC) Sp 83 (HC vs. all groups) AUC 0.93 |
| Model including FW in SCP and FA in SCP putamen, vermis, and corpus callosum | Se 93 (PD vs. MSA, PSP) Sp 93 (PD vs. MSA, PSP) AUC = 0.94 |
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| Model including FW in thalamus and cerebellar lobule V and FA in caudate nucleus | Se 95 (PD vs. MSA) Sp 89 (PD vs. MSA) AUC = 0.97 |
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| FW in SCP | Se 100 (PD vs. PSP) Sp 100 (PD vs. PSP) AUC = 1.00 |
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| Model including FW in pedunculopontine nucleus and subthalamic nucleus | Se 95 (MSA) Sp 95 (MSA vs. PSP) AUC = 0.97 |
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| Sako et al. (2016) | MSA-P 11/PD 36 | 1.5 and 3.0 T | Better AUC for MCP width and putaminal diffusivity Similar AUCs were seen in all patients with different disease duration and with different field strengths (1.5 or 3.0 T) |
MCP width | AUC = 0.93 (MSA-P vs. PD) |
| Putaminal diffusivity | AUC = 0.83 (MSA-P vs. PD) | ||||
| Cerebellar diffusivity | AUC = 0.73 (MSA-P vs. PD) | ||||
| Magnetization transfer imaging | |||||
| Eckert et al. (2004) | MSA 12/PD 15/PSP 10/HC 20 | 1.5 T | Change in the MTR in the globus pallidus, putamen, caudate nucleus, SN Stepwise linear discriminant analysis provided a good classification of the individual patients into the different disease groups |
Model including MTRs of globus pallidus, putamen and caudate nucleus (using stepwise linear discrimination model) | Overall correct classification 75% 95% of APD and 100% of non-APD classified correctly 75% of PD, 80% of HC, 58% of MSA and 90% of PSP classified correctly |
| Iron-sensitive sequences | |||||
| von Lewinski et al. (2007) | MSA 52/PD 88/HC 29 | 1.0 T | Signal loss of the dorsolateral putamen on T2* GE sequences in MSA Hyperintense lateral putaminal rim on FLAIR sequences MSA |
T2* Signal loss dorsolateral putamen | Se 69 (MSA) Sp 91 (vs. PD and HC) |
| T2* Hyperintense putaminal rim | Se 48 (MSA) Sp 93 (vs. PD and HC) |
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| T2* Signal loss dorsolateral putamen and hyperintense putaminal rim | Se 42 (MSA) Sp 97 (vs. PD and HC) |
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| SI PUT/CAUD | Se 65 (MSA) Sp 95 (vs. PD) |
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| Gupta et al. (2010) | MSA-P 12/PSP 12/PD 11 | 1.5 T | ↑ Red nucleus hypointensity in PSP compared to MSA-P and PD using SWI ↑ Putaminal hypointensity in PSP compared to PD using SWI No significant differences in putaminal hypointensity between PSP and MSA-P or MSA-P and PD using SWI |
SWI hypointensity score >2 (red nucleus) | Se 67 (PSP) Sp 82 (vs. PD) 83 (vs. MSA-P) |
| Arabia et al. (2010) | MSA 20/PSP 41/PD 189/HC 150 | 1.5 T | ↑ Frequencies of putaminal hypointensities in MSA-P and PSP compared to PD and HC using T2* GE sequences with 15 ms time echo | Putaminal hypointensitiesd | Se 55 (MSA), 25 (PD), 44 (PSP) Sp 93 (vs. HC) |
| Sakurai et al. (2010) | MSA-P 10/PD 14/HC 10 | 1.5 T | ↑ Grade of putaminal hypointensity in MSA-P compared to PD and HC on all 3D-PRESTO, T2*, and T2 sequences Significant differences in the mean grade of putaminal hypointensity in MSA-P among 3D-PRESTO, T2*, and T2 sequences |
Putaminal hypointensity (3D PRESTO)d | Se 90 (MSA-P) Sp 79 (vs. PD), 70 (vs. HC) |
| Putaminal atrophy (3D PRESTO)d | Se 70 (MSA-P) Sp 100 (vs. PD and HC) |
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| Wang et al. (2012a, b) | PD 16/MSA-P 8/HC 44 | 1.5 T | ↑ Iron content in putamen and thalamus in MSA-P vs. PD High-iron-deposition-percentage area provides slightly better accuracy than mean shift values |
High-iron-deposition-percentage area in putamen | AUC = 0.88 (MSA-P vs. PD) |
| High-iron-deposition-percentage area in pulvinar thalamus | AUC = 0.79 (MSA-P vs. PD) | ||||
| Han et al. (2013) | PSP 11/MSA-P 12/HC 20 | 3.0 T | ↑ Iron deposition in PSP and MSA-P vs. HC and PD ↑ Iron concentration of the red nucleus, SN, globus pallidus and thalamus in PSP vs. MSA-p ↑ Putaminal iron concentration in MSA vs. PSP ↑ Iron-related hypointense signals in the posterolateral putamen and adjacent lateral aspect of the globus pallidus in MSA-P ↑ Hypointense signals in the anterior and medial aspects of the globus pallidus and thalamus in PSP |
Putaminal mean phase shift values | AUC = 0.84 (MSA vs. PD and PSP) |
| Mean phase shift values in globus pallidus | AUC = 0.87 (PSP vs. PD and MSA) | ||||
| Mean phase shift values in thalamus | AUC = 0.88 (PSP vs. PD and MSA) | ||||
| Yoon et al. (2015) | PD 30/MSA-P 17 | 3.0 T | ↓ Signal intensity of bilateral posterior halves, mean values of the anterior and posterior halves, and the dominant-side posterior half of the putamen in MSA-P vs. PD | Signal intensity of the posterior part of putamen | AUC = 0.95 (MSA vs. PD) |
| Multimodal imaging | |||||
| Barbagallo et al. (2016) | PD 26/MSA 29 (MSA-P 16, MSA-C 13). | 3.0 T | Volume loss and both higher mean diffusivity values and T2* relaxation rates values in their putamina as well as higher caudate mean diffusivity values in MSA vs. PD No nigral changes between groups |
Combination of T2* relaxation rates values and MD in putamen | AUC = 0.96 (PD vs. MSA-P) |
APD atypical parkinsonian disorders, Se sensitivity, Sp specificity, AUC area under the curve, ↑ significant higher, ↓ significant lower, MSA multiple system atrophy, MSA-P parkinsonian variant of MSA, MSA-C cerebellar variant of MSA, PD Parkinson’s disease, PSP progressive supranuclear palsy, PSP-RS progressive supranuclear palsy-Richardson Syndrome, HC healthy controls, CBS corticobasal syndrome, MRI magnetic resonance imaging, T tesla, MCP middle cerebellar peduncle, SCP superior cerebellar peduncle, SN substantia nigra, DRTT dentatorubrothalamic tract, GE gradient echo, FLAIR fluid-attenuated inversion recovery, AUC area under the curve, ROI region of interest, DWI diffusion-weighted imaging, DTI diffusion tensor imaging, SWI susceptibility-weighted imaging, S/FC activity ratios of striatal to frontal cortex uptake, IBZM [123I]benzamide-SPECT imaging, HSR hemispheric symmetry ratio, ADC apparent diffusion coefficient, MD mean diffusivity, FA fractional anisotropy, FW free water, MTI magnetization transfer imaging, MTR magnetization transfer ratio, SI PUT/CAUD signal intensity dorsolateral putamen/signal intensity head of caudate nucleus
aIn the studies by Schocke et al. (2002) and Seppi et al. (2003, 2004), ADC was measured in z-slice direction only; in the other studies ADCs were averaged (ADCave) over three orthogonal measurements, thus representing the Trace (D) or diffusivity
bIncluding all patients studied by Schocke et al. (2002)
cIncluding all patients studied by Seppi et al. (2003)
dSensitivity and specificity refer to the qualitative inspection of iron-sensitive images