Korean J Radiol.  2018 Feb;19(1):93-100. 10.3348/kjr.2018.19.1.93.

In Vivo Assessment of Neurodegeneration in Type C Niemann-Pick Disease by IDEAL-IQ

• Guo RM
• Li QL
• Luo ZX
• Tang W
• Jiao J
• Wang J
• Kang Z
• Chen SQ
• Zhang Y

• KMID: 2425114
• DOI: http://doi.org/10.3348/kjr.2018.19.1.93

Abstract

OBJECTIVE
To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ).
MATERIALS AND METHODS
Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15-61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20-65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS.
RESULTS
Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7-4.9%, p < 0.05 and 1.8-3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2-2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2-3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS.
CONCLUSION
The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.

Keyword

Neurodegeneration; Magnetic resonance imaging; Magnetic resonance spectroscopy; Niemann-Pick type C disease

MeSH Terms

Brain
Female
Follow-Up Studies
Healthy Volunteers
Humans
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Methods
Niemann-Pick Diseases*
Proton Magnetic Resonance Spectroscopy
Water
Water

Figure

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  Fig. 1 35-year-old man with apathy, facial grimace, and limb dysmetria.Axial T1WI show hypo-intense signal (A), and axial T2WI (B) and T2-FLAIR image (C) show bilateral hyper-intensities in frontal-parietal periventricular white matters and corona radiata. Fat/water signal ratios of lesion (value A is 4.6) and surrounding normal appearing regions (value B is 2.9) in right corona radiata are measured from fat/water signal ratio image (D). T1WI = T1-weighted image, T2-FLAIR = T2-fluid attenuated inversion recovery, T2WI = T2-weighted image

• 

  Fig. 2 42-year-old man with apathy, dystonia, and hyperactive deep tendon reflexes.Axial T1WI show hypo-intense signal (A), and axial T2WI (B) and T2-FLAIR image (C) show unilateral hyper-intensities in left frontal periventricular white matters. The fat/water signal ratios of lesion (value A is 4.5) and contralateral normal appearing regions (value B is 1.7) are measured from fat/water signal ratio image. A1, A2, B1, and B2 is regions of interest for measuring lipid content in hyperintensities areas (D).

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  Fig. 3 Fat/water signal ratios of multiple parenchymal parts including frontal periventricular, parietal periventricular, corona radiata, centrum semiovale, hippocampus, temporal and occipital cortex in all subjects were quantitatively measured in fat/water signal ratio image of iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification sequence.Fat/water signal ratios of lesion regions (A) are higher than those of NARs in NPC group (B) and control group (C). In addition, fat/water signal ratios were also increased slightly in NARs of NPC group (B) than control group (C). *p < 0.05 compared with NARs in NPC group or control group, and compared between NARs in NPC group and control group. A = lesion regions in NPC group, B = normal appearing regions in NPC group, C = normal appearing regions in control group, NARs = normal appearing regions, NPC = Niemann-Pick type C disease

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  Fig. 4 Fat/water signal ratios of multiple parenchymal parts including frontal periventricular, parietal periventricular, corona radiata, centrum semiovale, hippocampus, temporal and occipital cortex in all subjects were quantitatively measured in fat/water signal ratio image of iterative decomposition of water and fat with echo asymmetry and least square estimation iron quantification sequence on admission and after two months.Fat/water signal ratios of lesion regions on admission (A) are higher than same location-matched fat/water signal ratios after two months (B). *p < 0.05 compared with same location-matched fat/water signal ratios after two months. A = lesion regions on admission, B = lesion regions after two months

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  Fig. 5 Lipid peak and fat/water signal ratios of multiple parenchymal parts including frontal periventricular, parietal periventricular, corona radiata, centrum semiovale, hippocampus, temporal and occipital cortex in NPC group were quantitatively measured in 1H-proton magnetic resonance spectroscopy and fat/water signal ratio image of IDEAL-IQ sequence on admission.Quantitative data of lipid peak (left Y axis) in lesion regions are higher than those in NARs, and fat/water signal ratios (right Y axis) of same location-matched lesion regions are higher than those of same location-matched NARs in NPC group. *p < 0.05 compared with NARs in NPC group, normal appearing regions in NPC group. IDEAL-IQ = iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification, Lip = lipid

• 

  Fig. 6 Lipid peak and fat/water signal ratios of multiple parenchymal parts including frontal periventricular, parietal periventricular, corona radiata, centrum semiovale, hippocampus, temporal and occipital cortex in all subjects were quantitatively measured in 1H-proton magnetic resonance spectroscopy and fat/water signal ratio image of IDEAL-IQ sequence.Fat/water signal ratios (right Y axis) of NARs in NPC group are higher than those of control group. Additionally, quantitative data of lipid peak (left Y axis) showed no significant difference between NARs of NPC and control groups. *p < 0.05 compared between NARs in NPC group and control group.

Reference

1. Yang CC, Su YN, Chiou PC, Fietz MJ, Yu CL, Hwu WL, et al. Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C. J Neurol Neurosurg Psychiatry. 2005; 76:592–595. PMID: 15774455.

2. Brady RO, Filling-Katz MR, Barton NW, Pentchev PG. Niemann-Pick disease types C and D. Neurol Clin. 1989; 7:75–88. PMID: 2646522.

3. Fink JK, Filling-Katz MR, Sokol J, Cogan DG, Pikus A, Sonies B, et al. Clinical spectrum of Niemann-Pick disease type C. Neurology. 1989; 39:1040–1049. PMID: 2761697.

4. Vanier MT. Phenotypic and genetic heterogeneity in Niemann-Pick disease type C: current knowledge and practical implications. Wien Klin Wochenschr. 1997; 109:68–73. PMID: 9060145.

5. Imrie J, Vijayaraghaven S, Whitehouse C, Harris S, Heptinstall L, Church H, et al. Niemann-Pick disease type C in adults. J Inherit Metab Dis. 2002; 25:491–500. PMID: 12555942.

6. Sévin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, et al. The adult form of Niemann-Pick disease type C. Brain. 2007; 130:120–133. PMID: 17003072.

7. Griffin LD, Gong W, Verot L, Mellon SH. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med. 2004; 10:704–711. PMID: 15208706.

8. Park M, Moon WJ. Structural MR imaging in the diagnosis of Alzheimer's disease and other neurodegenerative dementia: current imaging approach and future perspectives. Korean J Radiol. 2016; 17:827–845. PMID: 27833399.

9. Ma J, Song Z, Yan F. Detection of hepatic and pancreatic fat infiltration in type II diabetes mellitus patients with IDEAL-Quant using 3.0T MR: comparison with single-voxel proton spectroscopy. Chin Med J (Engl). 2014; 127:3548–3552. PMID: 25316227.

10. Kim H, Taksali SE, Dufour S, Befroy D, Goodman TR, Petersen KF, et al. Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL. Magn Reson Med. 2008; 59:521–527. PMID: 18306404.

11. Hofstetter LW, Yeo DT, Dixon WT, Kempf JG, Davis CE, Foo TK. Fat-referenced MR thermometry in the breast and prostate using IDEAL. J Magn Reson Imaging. 2012; 36:722–732. PMID: 22581513.

12. Tedeschi G, Bonavita S, Barton NW, Betolino A, Frank JA, Patronas NJ, et al. Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease. J Neurol Neurosurg Psychiatry. 1998; 65:72–79. PMID: 9667565.

13. Galanaud D, Tourbah A, Lehéricy S, Leveque N, Heron B, Billette de Villemeur T, et al. 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. 2009; 96:55–58. PMID: 19013089.

14. Sylvain M, Arnold DL, Scriver CR, Schreiber R, Shevell MI. Magnetic resonance spectroscopy in Niemann-Pick disease type C: correlation with diagnosis and clinical response to cholestyramine and lovastatin. Pediatr Neurol. 1994; 10:228–232. PMID: 8060425.

15. Zaaraoui W, Crespy L, Rico A, Faivre A, Soulier E, Confort-Gouny S, et al. In vivo quantification of brain injury in adult Niemann-Pick disease Type C. Mol Genet Metab. 2011; 103:138–141. PMID: 21397539.

16. Robertson DM, van Amelsvoort T, Daly E, Simmons A, Whitehead M, Morris RG, et al. Effects of estrogen replacement therapy on human brain aging: an in vivo 1H MRS study. Neurology. 2001; 57:2114–2117. PMID: 11739837.

17. Harzer K, Schlote W, Peiffer J, Benz HU, Anzil P. Neurovisceral lipidosis compatible with Niemann-Pick disease type C: morphological and biochemical studies of a late infantile case and enzyme and lipid assays in a prenatal case of the same family. Acta Neuropathol. 1978; 43:97–104. PMID: 209660.

18. Ong WY, Kumar U, Switzer RC, Sidhu A, Suresh G, Hu CY, et al. Neurodegeneration in Niemann-Pick type C disease mice. Exp Brain Res. 2001; 141:218–231. PMID: 11713633.

19. German DC, Liang CL, Song T, Yazdani U, Xie C, Dietschy JM. Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience. 2002; 109:437–450. PMID: 11823057.

20. Ren AJ, Guo Y, Tian SP, Shi LJ, Huang MH. MR imaging of the spine at 3.0T with T2-weighted IDEAL fast recovery fast spin-echo technique. Korean J Radiol. 2012; 13:44–45. PMID: 22247635.