MR Quantitative Susceptibility Imaging for the Evaluation of Iron Loading in the Brains of Patients with  -Thalassemia Major

Qiu, Deqiang; Chan, Godfrey C. F.; Chu, Jianping; Chan, Queenie; Ha, Sy; Moseley, Michael E.; Khong, Pek Lan

doi:10.3174/ajnr.a3849

Cited by 37 publications

(35 citation statements)

References 27 publications

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“…We investigated hemispheric location, gender and age‐related effects on iron content in healthy East‐Asian adults using the QSM method. Regional iron levels ranking from the highest to the lowest were found in the globus pallidus, substantia nigra, red nucleus, caudate nucleus and putamen, and thalamus, which agreed well with published QSM studies that investigated healthy subjects and biochemical studies of postmortem brain tissue .…”

Section: Discussionsupporting

confidence: 88%

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Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping

et al. 2015

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The purpose of this work was to investigate the effects of hemispheric location, gender and age on susceptibility value, as well as the association between susceptibility value and diffusional metrics, in deep gray matter. Iron content was estimated in vivo using quantitative susceptibility mapping. Microstructure was probed using diffusional kurtosis imaging. Regional susceptibility and diffusional metrics were measured for the putamen, caudate nucleus, globus pallidus, thalamus, substantia nigra and red nucleus in 42 healthy adults (age range 25-78 years). Susceptibility value was significantly higher in the left than the right side of the caudate nucleus (P = 0.043) and substantia nigra (P < 0.001). Women exhibited lower susceptibility values than men in the thalamus (P < 0.001) and red nucleus (P = 0.032). Significant age-related increases of susceptibility were observed in the putamen (P < 0.001), red nucleus (P < 0.001), substantia nigra (P = 0.004), caudate nucleus (P < 0.001) and globus pallidus (P = 0.017). The putamen exhibited the highest rate of iron accumulation with aging (slope of linear regression = 0.73 × 10(-3) ppm/year), which was nearly twice those in substantia nigra (slope = 0.40 × 10(-3) ppm/year) and caudate nucleus (slope = 0.39 × 10(-3) ppm/year). Significant positive correlations between the susceptibility value and diffusion measurements were observed for fractional anisotropy (P = 0.045) and mean kurtosis (P = 0.048) in the putamen without controlling for age. Neither correlation was significant after controlling for age. Hemisphere, gender and age-related differences in iron measurements were observed in deep gray matter. Notably, the putamen exhibited the highest rate of increase in susceptibility with aging. Correlations between susceptibility value and microstructural measurements were inconclusive. These findings could provide new clues for unveiling mechanisms underlying iron-related neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 88%

“…It is reported that in deep gray matter a positive linear correlation exists between magnetic susceptibility and iron content measured using x‐ray fluorescence imaging . Clinically, promising results have also been shown in investigations of patients with β ‐thalassemia, multiple sclerosis and Parkinson's disease .…”

Section: Introductionmentioning

confidence: 97%

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping

et al. 2015

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“…This is also supported by a study that showed evidence of iron overload in brain structures such as the putamen, dentate nucleus, substantia nigra and red nucleus of patients with beta-thalassemia[32]. Another group of patients with thalassemia also showed iron overload and increased oxidative damage[33].…”

Section: Discussionsupporting

confidence: 57%

Brain-derived neurotrophic factor plasma levels and premature cognitive impairment/dementia in type 2 diabetes

Ortíz¹,

Ramı́rez-Emiliano²,

Ramos-Rodríguez³

et al. 2016

WJD

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AIMTo assess the relationship of brain-derived neurotrophic factor (BDNF) with cognitive impairment in patients with type 2 diabetes.METHODSThe study included 40 patients with diabetes mellitus type 2 (DM2), 37 patients with chronic kidney disease in hem dialysis hemodialysis therapy (HD) and 40 healthy subjects. BDNF in serum was quantified by ELISA. The Folstein Mini-Mental State Examination was used to evaluate cognitive impairment.RESULTSThe patients with DM2 and the patients in HD were categorized into two groups, with cognitive impairment and without cognitive impairment. The levels of BDNF showed significant differences between patients with DM2 (43.78 ± 9.05 vs 31.55 ± 10.24, P = 0.005). There were no differences between patients in HD (11.39 ± 8.87 vs 11.11 ± 10.64 P = 0.77); interestingly, ferritin levels were higher in patients with cognitive impairment (1564 ± 1335 vs 664 ± 484 P = 0.001). The comparison of BDNF values, using a Kruskal Wallis test, between patients with DM2, in HD and healthy controls showed statistical differences (P < 0.001).CONCLUSIONLow levels of BDNF are associated with cognitive impairment in patients with DM2. The decrease of BDNF occurs early and progressively in patients in HD.

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“…On the other hand, a few MRI studies have suggested a possible brain tissue iron overload as a possible pathogenic mechanism of brain injury. However, using a dedicated MRI protocol and an advanced voxel‐based quantitative MRI analysis, no iron overload was observed in the brain tissue of beta‐thalassaemia patients, but in the choroid plexuses (Qiu et al , ), revealing that the blood brain barrier efficiently protects the central nervous system from the persistently high systemic iron levels that characterize beta‐thalassaemia. The present study went a step further and investigated possible relationships between cognitive performances and either the white matter abnormality burden on conventional MRI, the intracranial vessel changes on conventional MRA and the iron load quantified with a dedicated MRI protocol and subsequent advanced MRI analysis.…”

Section: Discussionmentioning

confidence: 99%

Brain functional impairment in beta‐thalassaemia: the cognitive profile in Italian neurologically asymptomatic adult patients in comparison to the reported literature

et al. 2019

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Summary Cognitive involvement in beta‐thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically‐asymptomatic beta‐thalassaemia patients (mean‐age 34·5 ± 10·3 years; 53 transfusion‐dependent [TDT], 21 non‐transfusion dependent [NTDT]) and 45 healthy volunteers (mean‐age 33·9 ± 10·7 years). Participants underwent testing with Wechsler Adult Intelligence Scale‐Fourth Edition (WAIS‐IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T‐magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full‐Scale Intelligence Quotient (FSIQ) than controls (75·5 ± 17·9 vs. 97·4 ± 18·1, P < 0·0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P = 0·08) but a similar cognitive profile at WAIS‐subtests. FSIQ correlated with total and indirect bilirubin (P < 0·0001 and P = 0·002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance‐angiography findings, brain tissue iron content or other disease‐related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28·74 ± 3·1 vs. 27·29 ± 4·8, P = 0·01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84·4% vs. 64·9%, P = 0·004) and correlated with higher FSIQ (P = 0·001) and education level (P = 0·001). In conclusion, Italian adult beta‐thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long‐term socio‐economic consequences.

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MR Quantitative Susceptibility Imaging for the Evaluation of Iron Loading in the Brains of Patients with -Thalassemia Major

Cited by 37 publications

References 27 publications

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping

Brain-derived neurotrophic factor plasma levels and premature cognitive impairment/dementia in type 2 diabetes

Brain functional impairment in beta‐thalassaemia: the cognitive profile in Italian neurologically asymptomatic adult patients in comparison to the reported literature

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