Neuroimaging features of neurodegeneration with brain iron accumulation

NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.     

MRI of brain iron

A prominently decreased signal intensity in the globus pallidum, reticular substantia nigra, red nucleus, and dentate nucleus was routinely noted in 150 consecutive individuals on T2-weighted images (SE 2000/100) using a high field strength (1.5 T)MR system. This MR finding correlated closely with the decreased estimated T2 relaxation times and the sites of preferential accumulation of ferric iron using the Perls staining method on normal postmortem brains. The decreased signal intensity on T2-weighted images thus provides an accurate in vivo map of the normal distribution of brain iron. Perls stain and MR studies in normal brain also confirm an intermediate level of iron distribution in the striatum, and still lower levels in the cerebral gray and white matter. In the white matter, iron concentration is (a) absent in the most posterior portion of the internal capsule and optic radiations, (b) higher in the frontal than occipital regions, and (c) prominent in the subcortical "U" fibers, particularly in the temporal lobe. There is no iron in the brain at birth; it increases progressively with aging. Knowledge of the distribution of brain iron should assist in elucidating normal anatomic structures and in understanding neurodegenerative, demyelinating, and cerebrovascular disorders.     

MRI of primary spleen angiosarcoma with iron accumulation.

A case of splenic angiosarcoma with siderotic nodules is reported. The tumor was hyperechoic on ultrasound and had high density on CT and very low intensity on MR. Gandy-Gamna nodules (siderotic nodules) were demonstrated histopathogically.     

Missense PANK2 mutation without "eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN)

Purpose:

To present some unusual MR findings in a group of patients from the south‐west of the Dominican Republic suffering from Pantothenate Kinase Associated Neurodegeneration (PKAN).

Materials and Methods:

Twenty patients and one preclinical case homozygous for the PANK2 mutation, 13 heterozygous gene carriers and 14 healthy volunteers were scanned prospectively using a 3 Tesla system.

Results:

All patients showed the typical signal reduction within the globus pallidus and the substantia nigra. A surprising finding was the absence of the bright spot (“tiger's eye”) in the medial part of the pallidum in 6 patients, but not in the preclinical case. Both fractional anisotropy (FA) and mean diffusivity (MD) were increased with high significance in the globus pallidus, whereas a reduction of FA in the anterior parts of the internal capsule was accompanied by an elevation of MD.

Conclusion:

Our findings support the hypothesis that the absence of the “tiger's eye” in PKAN might be secondary, probably caused by an increased accumulation of iron. This could artificially increase FA and MD values and change fiber tracking results. Except for the fronto‐basal tracts, white matter was preserved well. This encouraging finding might support efforts to develop further therapeutic strategies in this devastating dystonia. J. Magn. Reson. Imaging 2012;35:788–794. © 2011 Wiley Periodicals, Inc.     

Multi-modal quantitative MRI investigation of brain tissue neurodegeneration in multiple sclerosis

Purpose:

To investigate the utility of multimodal quantitative MRI (qMRI) and atlas‐based methods to identify characteristics of lesion‐driven injury and neurodegeneration in relapsing remitting multiple sclerosis (RRMS).

Materials and Methods:

This work is health insurance portability and accountability act compliant. High resolution T1‐weighted, dual echo, and fluid‐attenuated inversion recovery and diffusion tensor MRI images were prospectively acquired on 68 RRMS patients (range, 25–58 years) and 68 age‐matched controls. The data were analyzed using standardized human brain atlas‐based tissue segmentation procedures to obtain regional volumes and their corresponding T2 relaxation times and DTI maps.

Results:

Group‐averaged brain atlas‐based qMRI maps of T2, fractional anisotropy and diffusivities are visually presented and compared between controls and RRMS. The analysis shows a widespread injury in RRMS. Atrophy of the corpus callosum (CC) was substantial in RRMS. The qMRI attributes of the neocortex in combination with the CC such as T2 and diffusivities were elevated and correlated with disability.

Conclusion:

Using a standardized multimodal qMRI acquisition and analyses that accounted for lesion distribution we demonstrate that cerebral pathology is widespread in RRMS. Our analysis of CC and neocortex qMRI metrics in relation to disability points to a neurodegenerative injury component that is independent from lesions. J. Magn. Reson. Imaging 2012;35:1300–1311. © 2012 Wiley Periodicals, Inc.     

簇状钙化对乳腺触诊阴性的良恶性病变的鉴别诊断价值

目的:总结分析脑内铁沉积性神经变性病(NBIA)的MRI表现。方法:回顾性分析3例NBIA患者的MRI表现,3例均行颅脑常规MRI检查,其中2例加行磁敏感加权成像(SWI)扫描。结果:3例患者在T2WI扫描序列上均示双侧苍白球较低信号,边界较清,在低信号的内部对称出现斑点状高信号,即"虎眼征"。SWI幅度图可见双侧苍白球呈极低信号,SWI相位图上"虎眼征"更加明显。结论:T2WI苍白球区域出现"虎眼征"是NBIA的特异性征象,SWI幅度图能更清晰地显示这一征象,SWI相位图能定量测量基底节区的铁沉积。     

Progressive brain iron accumulation in neuroferritinopathy measured by the thalamic t2* relaxation rate

SUMMARY: Neuroferritinopathy is an autosomal dominant extrapyramidal movement disorder, caused by FTL gene mutations. Iron decreases the MR T2* decay time, therefore increasing the R2* (R2* = 1 /T2*), which correlates with brain tissue iron content. 3T structural and quantitative MR imaging assessment of R2* in 10 patients with neuroferritinopathy demonstrated a unique pattern of basal ganglia cavitation involving the substantia nigra in older patients and increasing thalamic R2* signal intensity detectable during 6 months. Increasing R2* signal intensity in the thalamus correlated with progression on a clinical rating scale measuring dystonia severity. Thalamic R2* signal intensity is a clinically useful method of objectively tracking disease progression in this form of neurodegeneration with brain iron accumulation.     

Brain abscess and cystic brain tumor: discrimination with dynamic susceptibility contrast perfusion-weighted MRI

Differentiating between brain abscesses and cystic brain tumors such as high-grade gliomas and metastases is often difficult with conventional MRI. The goal of this study was to evaluate the diagnostic utility of perfusion MRI to differentiate between these pathologies. MRI was performed in 19 patients with rim-enhancing brain lesions (4 pyogenic abscesses, 8 high-grade gliomas, 7 metastases). In addition to standard MR sequences, trace diffusion-weighted MRI with apparent diffusion coefficient (ADC) maps and perfusion-weighted MRI by using a first-pass gadopentetate dimeglumine T2*-weighted gradient echo single-shot echo-planar sequence were performed. Relative cerebral blood volume (rCBV) ratios were obtained via the values of the capsular portions of the lesions and the normal white matter. All the abscesses had markedly hyperintense signals in trace diffusion images, whereas they had significant hypointense signals in ADC images. In perfusion-weighted images, the capsular portions of the abscesses demonstrated low colored areas compared with the normal white matter and the rCBV ratio calculated was 0.76 +/- 0.12 (mean +/- SD). All but two of the cystic tumors showed low signal intensity on trace diffusion-weighted images and high signal intensity on ADC maps. Hyperintense signal was found in two brain tumors mimicking brain abscesses on trace diffusion images. The rCBV values in high-grade gliomas and metastases were 5.51 +/- 2.08 and 4.58 +/- 2.19, respectively. The difference between abscesses and cystic tumors was statistically significant (P = 0.003). Perfusion MRI may allow the differentiation of pyogenic brain abscess from cystic brain tumors, making it a strong additional imaging modality in the early diagnosis of these two entities.     

Whole brain functional connectivity in clinically isolated syndrome without conventional brain MRI lesions

Objective

To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up.

Methods

We recruited 20 CIS patients without conventional brain lesions, 28 patients with MS and 28 healthy controls (HC). Normalized voxel-based functional connectivity strength (nFCS) was determined using resting-state fMRI (R-fMRI) and compared among groups. Furthermore, 5-years clinical follow-up of the CIS patients was performed to examine the differences in nFCS between converters and non-converters.

Results

Compared to HC, CIS patients showed significantly decreased nFCS in the visual areas and increased nFCS in several brain regions predominately in the temporal lobes. MS patients revealed more widespread higher nFCS especially in deep grey matter (DGM), compared to CIS and HC. In the four CIS patients converting to MS, significantly higher nFCS was found in right anterior cingulate gyrus (ACC) and fusiform gyrus (FG), compared to non-converted patients.

Conclusion

We demonstrated both functional impairment and compensation in CIS by R-fMRI. nFCS alteration in ACC and FG seems to occur in CIS patients at risk of developing MS.

Key Points

? Both functional impairment and compensation occur in CIS without conventional brain lesions. ? MS patients revealed more widespread higher nFCS especially in deep grey matter. ? nFCS alteration may help stratifying CIS at risk of developing MS.

     

磁共振新技术评估阿尔茨海默病脑内铁沉积

越来越多的研究证明阿尔茨海默病(AD)有脑内铁的代谢紊乱、脑铁沉积增加,且脑内铁的过量沉积与氧化应激及β淀粉样变密切相关,与AD的发生和病情的进展关系密切。MRI可以无创性地检查脑内铁的变化,因而对AD的发病机制、早期诊断及动态监测病情变化具有重要价值。就目前所采用的AD脑铁测量的各种MRI序列及其优缺点进行综述,并介绍尚未应用于AD的定量测量脑铁的新技术。     

Direct saturation MRI: Theory and application to imaging brain iron

When applying RF saturation to tissue, MRI signal reductions occur due to magnetization transfer (MT) and direct saturation (DS) effects on water protons. It is shown that the direct effects, often considered a nuisance, can be used to distinguish gray matter (GM) regions with different iron content. DS effects were selected by reducing the magnitude and duration of RF irradiation to minimize confounding MT effects. Contrary to MT saturation spectra, direct water saturation spectra are characterized by a symmetric Lorentzian‐shaped frequency dependence that can be described by an exact analytical solution of the Bloch equations. The effect of increased transverse relaxation, e.g., due to the presence of iron, will broaden this saturation spectrum. As a first application, DS ratio (DSR) images were acquired to visualize GM structures in the human brain. Similar to T₂^*‐weighted images, the quality of DSR images was affected by local field inhomogeneity, but this could be easily corrected for by centering the saturation spectrum on a voxel‐by‐voxel basis. The results show that, contrary to commonly used T₂^*‐weighted and absolute R₂ images, the DSR images visualize all GM structures, including cortex. A direct correlation between DSR and iron content was confirmed for these structures. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Echo-planar and gradient-echo diffusion MRI of normal brain iron in the globus pallidus

The purpose of this study was to investigate effects of normal brain iron on proton diffusion and its quantification by diffusion MRI. The studies were undertaken in 24 cases ages ranging from 15 to 74 years (mean=45 years) with normal iron deposition in the globus pallidus to characterize the appearances on diffusion imaging with differing b values and on apparent diffusion coefficient (ADC) maps. Diffusion MRI was obtained by the spin-echo echo-planar imaging sequence (n=20 patients) or by the gradient-echo diffusion sequence, PSIF (n=4). In the PSIF sequence, pixel lens calculations were performed. In the echo-planar sequence, ADC value calculations were performed by using Stejskal–Tanner formula and by direct reading from automatically generated ADC maps. ADC values obtained from the normal appearing parenchyma were used as controls. Twenty patients with acute cerebral infarction were included for comparison of ADC values with those of iron deposition. The mean ADC value in the normal cerebral parenchyma was 0.85±0.11×10⁻³ mm²/s. In the globus pallidus, mean ADC value was 48±0.12×10⁻³ mm²/s. That of regions with acute infarction was 0.34±0.11×10⁻³ mm²/s. On b=0 or 50, b=500 and b=1000 s/mm² images of the echo-planar diffusion imaging globus pallidus appeared hypointense compared to surrounding parenchymal structures. Low signal and low pixel values were evident on the PSIF imaging. This study indicates that, on diffusion MRI, normal iron deposition reveals prominent low signal on all the images of the echo-planar diffusion imaging sequence with differing b values, as well as on the gradient-echo diffusion, PSIF sequence. Low signal on ADC maps and low ADC values are evident. These represent characteristic diffusion MRI features of normal iron deposition in the brain, reflecting susceptibility effects.     

Assessment of relative brain iron concentrations using T2-weighted and T2*-weighted MRI at 3 Tesla

In this paper a new method is presented for the relative assessment of brain iron concentrations based on the evaluation of T₂ and T₂* -weighted images. A multiecho sequence is employed for rapid measurement of T₂ and T₂*, enabling calculation of the line broadening effect ( T₂′). Several groups have failed to show a correlation between T₂ and brain iron content. However, quantification of T₂′, and the associated relaxation rate R₂′, may provide a more specific relative measure of brain iron concentration. This may find application in the study of brain diseases, which cause associated changes in brain iron levels. A new method of field inhomogeneity correction is presented that allows the separation of global and local field inhomogeneities, leading to more accurate T₂* measurements and hence, T₂′ values. The combination of T₂*, and T₂-weighted MRI methods enables the differentiation of Parlkinson's disease patients from normal age-matched controls based on differences in iron content within the substantia nigra.     

Brain MRI with laser-polarized 129xe

The feasibility of brain MRI with laser-polarized ¹²⁹Xe in a small animal model is demonstrated. Naturally abundant ¹²⁹Xe is polarized and introduced into the lungs of Sprague-Dawley rats. Polarized xenon gas dissolves in the blood and is transported to the brain where it accumulates in brain tissue. Spectroscopic studies reveal a single, dominant, tissue-phase NMR resonance in the head at 194.5 ppm relative to the gas phase resonance. Images of ¹²⁹Xe in the rat head were obtained with 98-μl voxels by 2D chemical shift imaging and show that xenon is localized to the brain. This work establishes that nuclear polarization produced in the gas phases survives transport to the brain where it may be imaged. Increases in polarization and delivered volume of ¹²⁹Xe will allow clinical measurements of regional cerebral blood flow.     

神经退行性疾病脑铁负荷的MRI测量研究

铁是人体内含量最多的金属元素,在正常功能的神经元中起关键作用。铁缺乏与铁过载均可导致神经退行性疾病。神经退行性疾病中的不宁腿综合征可发现脑铁含量的减低,而阿尔茨海默病、帕金森病、亨廷顿病、多发性硬化、肌萎缩脊髓侧索硬化症等疾病发病过程都伴有铁过载。了解神经退行性疾病脑铁含量的变化对于早期疾病的诊断及临床治疗具有重要的指导意义。综述不同神经退行性疾病的脑铁含量的空间变化特点。     

Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury

PURPOSE: To determine the change over time of the apparent diffusion coefficient (ADC) and relative anisotropy of cerebral water in a cohort of premature newborns serially studied near birth and again near term. MATERIALS AND METHODS: Newborns were classified as normal (N = 11), minimal white matter injury (N = 7), or moderate white matter injury (N = 5). RESULTS: ADC decreased significantly with age in all brain regions in newborns classified as normal and those with minimal white matter injury. ADC increased with age or failed to decline in widespread areas of white matter in newborns with moderate white matter injury. Anisotropy increased with age in all white matter regions in newborns classified as normal. Anisotropy did not increase in frontal white matter in those with minimal white matter injury, and in widespread white matter areas in those with moderate white matter injury. CONCLUSION: This study demonstrates that serial diffusion tensor magnetic resonance imaging scans of premature newborns can detect differences in white matter maturation in infants with and without white matter injury.