Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron

The distribution of iron in the brain was analyzed using high field strength (1.5 T) magnetic resonance (MR) imaging in 14 healthy control individuals and six patients with Parkinson plus syndromes (multisystem atrophy and progressive supranuclear palsy) who were unresponsive to antiparkinsonian therapy. The normal topographic distribution of iron in the brain as indicated by high field MR images coincided precisely with the distribution of iron in the brain as determined by Perls staining for ferric iron. In Parkinson plus syndromes, there were abnormally increased concentrations of iron (decreased T2 relaxation times) in the putamen, and less prominent increases in the caudate nucleus and lateral pars compacta of the substantia nigra. In high field strength MR images of normal patients, the decreased signal intensity in the globus pallidus is more prominent than that of the putamen. In MR images of patients with Parkinson plus syndromes, the decreased signal intensity of the putamen is more prominent than that of the globus pallidus.     

Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths

The authors measured in vivo signal intensity on magnetic resonance (MR) images and postmortem iron concentrations in the brains of three young and two old rhesus monkeys. T2-weighted MR imaging was done at 0.5, 1.5, 2.0, and 4.7 T. Relative assessment of iron concentration was made from the optical density of brain sections stained with the Perls' method intensified with diaminobenzidine. MR imaging and optical density measurements were made in the centrum semiovale (white matter) and in four gray matter areas: the insular cortex, caudate nucleus, putamen, and globus pallidus, the latter three of which accumulate significant iron deposits with age. High optical density and decreased signal intensity were found in these areas, and the inverse correlation between gray matter/white matter signal ratio and optical density was in good agreement with the theory of T2 shortening caused by diffusion of water through magnetic inhomogeneities. However, the dependence of T2 shortening on field strength was not quadratic, as expected for paramagnetic iron, but instead showed a marked leveling off at higher field strengths. This magnetic "saturation" is explainable by antiferromagnetism and superparamagnetism of the ferritin core and has been observed in ferritin solutions at low temperatures. Similar observations at body temperature are needed before the iron-ferritin explanation for T2 shortening can be considered proved.     

Membranous lipodystrophy: MR imaging appearance of the brain

Five patients with membranous lipodystrophy (lipomembranous polycystic osteodysplasia with progressive dementia) underwent magnetic resonance (MR) imaging of the brain. T2-weighted MR images showed atrophied cerebral white matter with dilated ventricles; increased signal intensity of the white matter; and decreased signal intensity of the thalamus, putamen, caudate nucleus, and cerebral cortex. Although each single finding is not specific, the combination of the above MR findings when coupled with skeletal lesions strongly suggests this rare disease.     

Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: increased iron content?

High-field-strength (1.5-T) MR imaging was used to evaluate 47 patients with definite multiple sclerosis and 42 neurologically normal control patients. Abnormal, multiple foci of increased signal intensity on T2-weighted images, most prominent in the periventricular white matter, were apparent in 43 of 47 MS patients and in two of 42 control patients. A previously undescribed finding of relatively decreased signal intensity most evident in the putamen and thalamus on T2-weighted images was seen in 25 of 42 MS patients and correlated with the degree of white-matter abnormality. In the normal control patients a prominently decreased signal intensity was noted in the globus pallidus, as compared with the putamen or thalamus, correlating closely with the distribution of ferric iron as determined in normal Perls'-stained autopsy brains. The decreased signal intensity (decreased T2) is due to ferritin, which causes local magnetic field inhomogeneities and is proportional to the square of the field strength. The decreased T2 in the thalamus and striatum in MS may be related to abnormally increased iron accumulation in these locales with the underlying mechanism remaining speculative.     

MR imaging of amyotrophic lateral sclerosis]

Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area.     

Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Our purpose was to investigate transient MR signal changes on periictal MR images of patients with generalized tonicoclonic seizure or status epilepticus and to evaluate the clinical significance of these findings for differential diagnosis and understanding of the pathophysiology of seizure-induced brain changes. METHODS: Eight patients with MR images that were obtained within 3 days after the onset of generalized tonicoclonic seizure or status epilepticus and that showed seizure-related MR signal changes had their records retrospectively reviewed. T1- and T2-weighted images were obtained of all eight patients. Additional diffusion-weighted images were obtained of five patients during initial examination. After adequate control of the seizure was achieved, follow-up MR imaging was performed. We evaluated the signal changes, location of the lesions, and degree of contrast enhancement on T1- and T2-weighted images and the signal change and apparent diffusion coefficient (ADC) on diffusion-weighted images. We also compared the signal changes of the initial MR images to those of the follow-up MR images. RESULTS: The initial MR images revealed focally increased T2 signal intensity, swelling, and increased volume of the involved cortical gyrus in all eight patients. The lesions were located in the cortical gray matter or subcortical white matter in seven patients and at the right hippocampus in one. T1-weighted images showed decreased signal intensity at exactly the same location (n = 6) and gyral contrast enhancement (n = 4). Diffusion-weighted images revealed increased signal intensity at the same location and focally reduced ADC. The ADC values were reduced by 6% to 28% compared with either the normal structure opposite the lesion or normal control. Follow-up MR imaging revealed the complete resolution of the abnormal T2 signal change and swelling in five patients, whereas resolution of the swelling with residual increased T2 signal intensity at the ipsilateral hippocampus was observed in the other two patients. For one of the two patients, hippocampal sclerosis was diagnosed. For the remaining one patient, newly developed increased T2 signal intensity was shown. CONCLUSION: The MR signal changes that occur after generalized tonicoclonic seizure or status epilepticus are transient increase of signal intensity and swelling at the cortical gray matter, subcortical white matter, or hippocampus on periictal T2-weighted and diffusion-weighted images. These findings reflect transient cytotoxic and vasogenic edema induced by seizure. The reversibility and typical location of lesions can help exclude the epileptogenic structural lesions.     

MR imaging of compact white matter pathways

A prominent decreased signal intensity can be seen in many of the heavily myelinated, compact fiber pathways of the brain on T2-weighted spin-echo MR images (TR = 2500 msec, TE = 80 msec). These areas include the anterior commissure, internal capsule, optic tract and radiations, fornix, mammillothalamic tract, superior frontooccipital fasciculus, cingulum, corpus callosum, uncinate fasciculus, and superior longitudinal fasciculus. All these pathways could be identified in normal subjects 3 years old and older when 1.5-T axial and coronal images of 50 adults and 17 children were reviewed. Correlation of the in vivo and postmortem MR appearance of two human brains with Perls and Luxol fast blue stains indicates that the short T2 reflects heavy myelination and fiber density, not iron deposition. This is in contrast to the short T2 signal seen in the subcortical U fibers and deep nuclei of the brain that result from iron deposition. These pathways also differ from areas of brain iron accumulation in that (1) they may appear as areas of short T1 on partial-saturation or inversion-recovery pulse sequences and (2) they can be seen with regularity in all patients over 3 years of age. It is important to distinguish between the effect of the myelin sheath and the effect of brain iron on the T2 relaxation values seen in the normal brain since both result in shortened T2 relaxation. The importance of the role of these fiber tracts in disease processes and in modifying the spread of vasogenic edema and tumor needs further investigation.     

Pantothenate kinase-associated neurodegeneration: MR imaging,proton MR spectroscopy,and diffusion MR imaging findings

We herein report the case of a 15-year-old male patient with pantothenate kinase-associated neurodegeneration. The classic "eye-of-the-tiger" appearance was initially present on the globus pallidi on T2-weighted MR images and had disappeared by the time of the 10-month follow-up examination. Fluid-attenuated inversion recovery images revealed marked hypointensity in the globus pallidi and dentate nuclei and high signal intensity changes in the deep cerebral white matter. Proton MR spectroscopy revealed markedly decreased N-acetylaspartate in the globus pallidi, associated with decreased N-acetylaspartate and increased myoinositol in the deep cerebral white matter. Diffusion MR images (b=1000 s/mm(2)) were negative (normal appearing) for deep cerebral white matter lesions, whereas apparent diffusion coefficient values were slightly increased (1.08-1.12 x 10(-3) mm(2)/s), compared with the apparent diffusion coefficient values from the normal white matter regions. Apparent diffusion coefficient values in the globus pallidi were lower than those in the unaffected thalamus.     

Magnetic resonance imaging and histologic findings of experimental cerebral fat embolism

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether cerebral fat embolism demonstrated reversible or irreversible findings in magnetic resonance (MR) imaging over time and to compare the features in MR images with histologic findings in a cat model. MATERIALS AND METHODS: MR images were obtained serially at 2 hours, 1 and 4 days, and 1, 2, and 3 weeks after embolization with 0.05 mL of triolein into the internal carotid artery in 19 cats. Any abnormal signal intensity and change in the signal intensity were evaluated on T2-weighted images, T1-weighted images, diffusion-weighted images (DWIs; including apparent diffusion coefficient [ADC] maps), and gadolinium-enhanced T1-weighted images (Gd-T1WI) over time. After MR imaging at 3 weeks, brain tissue was obtained and evaluated for light microscopic (LM) examination using hematoxylin-eosin and Luxol fast blue staining. For electron microscopic examination, the specimens were obtained at the cortex. The histologic and MR findings were compared. RESULTS: The embolization lesions showed hyperintensity on T2-weighted images, hyperintensity, or isointensity on DWIs, hypointensity, or isointensity on ADC maps and contrast enhancement on Gd-T1WIs at 2 hours. The T2-weighted hyperintensity extended to the white matter at day 1 and decreased thereafter. Contrast enhancement decreased continuously from day 1, and hyperintensity on DWI decreased after day 4. Hypointensity on ADC maps became less prominent after day 4. By week 3, most lesions had reverted to a normal appearance on MR images and were correlated with LM findings. However, small focal lesions remained in the gray matter of 8 cats and in the white matter of 3 cats on MR images, and this correlated with the cystic changes on LM findings. Electron microscopic examination of the cortical lesions that reverted to normal at week 3 in MR images showed that most of these lesions appeared normal but showed sporadic intracapillary fat vacuoles and disruption of the endothelial walls. CONCLUSIONS: The embolized lesions of the hyperacute stage were of 2 types: type 1 lesions, showing hyperintensity on DWIs and hypointensity on ADC maps, have irreversible sequelae, such as cystic changes; whereas type 2 lesions, showing isointensity or mild hyperintensity on DWIs and ADC maps, reverted to a normal appearance in the subacute stage.     

Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors

OBJECTIVE: The aim of this study was to evaluate the characteristics of an ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain tumors and to correlate changes on MRI with histopathologic data collected systematically in all patients. SUBJECTS AND METHODS: Nine patients with brain tumors were imaged before and 24 hr after administration of a USPIO at a dose of 2.6 mg Fe/kg. Analysis of MR images included qualitative and quantitative comparison of the USPIO and gadolinium enhancement of brain tumors. Brain surgery was performed 25-112 hr after administration of the USPIO. The histopathologic workup included iron histochemistry with diaminobenzidine (DAB)-enhanced Perls stain. RESULTS: In seven of nine patients, USPIO-related changes of signal intensity were observed in gadolinium-enhancing brain tumors on T1- and T2*-weighted sequences. The difference in signal intensity on T1-weighted USPIO series was 40.1% +/- 26.7% (mean +/- SD). On T2*-weighted USPIO series, the difference in signal intensity was -33.1% +/- 18.4% in solid tumor parts. Areas of suspected radiation necrosis did not enhance in three patients with prior radiation therapy. Iron histochemistry revealed the presence of iron deposits in macrophages in two patients. CONCLUSION: USPIO agents will not replace gadolinium in the workup of patients with brain tumors. Our findings suggest that USPIO agents seem to offer complementary information and may help to differentiate between brain tumors and areas of radiation necrosis. Signal intensity changes on T2*-weighted images might be related to the blood pool properties of the agent, possibly reflecting steady-state susceptibility effects.     

Characteristics and pitfalls of contrast-enhanced, T1-weighted magnetization transfer images of the brain

RATIONALE AND OBJECTIVES: This study was undertaken to clarify the difference in signal pattern on contrast material-enhanced T1-weighted magnetic resonance (MR) magnetization transfer (MT) images between enhancing and nonenhancing lesions in various intracranial diseases and to determine the necessity of nonenhanced MT images for evaluating lesional contrast enhancement. MATERIALS AND METHODS: MR images of 116 patients who underwent nonenhanced T1-weighted imaging, nonenhanced MT imaging, and contrast-enhanced MT imaging were reviewed. The increase in signal intensity of lesions relative to normal brain was compared between nonenhanced T1-weighted images and contrast-enhanced MT images. Signal intensity of lesions was compared with that of the striate nucleus and white matter on contrast-enhanced MT images. True enhancement was determined by comparison with nonenhanced MT images. RESULTS: In all, 143 lesions, including 86 enhancing and 57 nonenhancing lesions, were identified among 63 patients. Almost all (99%) of the enhancing lesions were hyperintense to striate nucleus on contrast-enhanced MT images, and most (>87%) showed moderate to marked signal intensity increase from nonenhanced T1-weighted images to contrast-enhanced MT images. Most (>95%) of the nonenhancing lesions showed mild or no increase in relative signal intensity, and most (75%) were iso- or hypointense to striate nucleus on contrast-enhanced MT images. A few nonenhancing lesions (4%-6%), however, showed increase in signal intensity that was indistinguishable from true enhancement without comparison to non-enhanced MT images. CONCLUSION: Nonenhanced MT images should be obtained to assess pathologic enhancement accurately.     

Relationship between MR imaging and histopathologic findings of the brain in extremely sick preterm infants.

BACKGROUND AND PURPOSE: MR imaging can now be used safely in extremely preterm infants. The aim of this study was to compare the MR imaging appearance of the immature brain with neuropathologic findings at postmortem examination. METHODS: Seven extremely sick preterm infants, born at a median of 24 weeks' gestation, were studied using T1- and T2-weighted MR sequences. Infants died at a median of 3 days after initial MR imaging, and postmortem examinations were carried out. RESULTS: The cortex and germinal matrix were seen as areas of low signal intensity on T2-weighted images, which corresponded to their highly cellular histologic appearance. The periventricular and subcortical layers of white matter had a high signal intensity, corresponding to high fiber and relatively low cellular density; the intermediate layer of low signal intensity corresponded to a dense band of migrating cells. Regions of acute hemorrhage were seen as low signal intensity and regions of infarction as high signal intensity on T2-weighted images. One infant with mild periventricular leukomalacia had some low signal intensity on T1-weighted images, but no focal changes on T2-weighted images. Regions of neuronal mineralization, seen in association with infarction and capillary proliferation, within the basal ganglia and thalami were characterized by very low signal intensity on T2-weighted images and by very high signal intensity on T1-weighted images. There were no imaging abnormalities detected in regions with more subtle histologic abnormalities, such as increased glial or apoptotic cells. CONCLUSION: MR imaging can be used to observe normal developing brain anatomy in extremely premature infants; it can detect areas of hemorrhage and infarction within the developing brain, but conventional MR imaging may not detect more subtle histologic abnormalities.     

Nipah virus encephalitis: serial MR study of an emerging disease.

PURPOSE: To report the serial magnetic resonance (MR) imaging findings of the Nipah virus. MATERIALS AND METHODS: Twelve patients underwent serial MR imaging. Eight patients were examined at the outbreak; 11, at 1 month; and seven, at 6 months. Contrast material-enhanced MR images, diffusion-weighted images, and single-voxel proton MR spectroscopic images were reviewed. Clinical and neurologic assessment, as well as analysis of the size, location, and appearance of brain lesions on MR images, were performed. RESULTS: During the outbreak, all eight patients had multiple small foci of high signal intensity within the white matter on T2-weighted images. In six patients, cortical and brain stem lesions were also detected, and five patients had diffusion-weighted MR imaging-depicted hyperintensities. One month after the outbreak, five patients had widespread tiny foci of high signal intensity on T1-weighted images, particularly in the cerebral cortex. Diffusion-weighted images showed decreased prominence or disappearance of lesions over time. There was no evidence of progression or relapse of the lesions at 6-month follow-up. MR spectroscopy depicted reduction in N-acetylaspartate-to-creatine ratio and elevation of choline-to-creatine ratios. CONCLUSION: The Nipah virus has findings unlike other viral encephalitides: small lesions that are primarily within the white matter, with transient punctate cortical hyperintensities on T1-weighted images.     

Metastatic adenocarcinoma to the brain: MR with pathologic correlation.

PURPOSETo describe the appearance on T2-weighted scans of metastatic adenocarcinoma to the brain and to show that the hypointensity frequently associated with these lesions is not related to the presence of mucin, blood products, iron, or calcium.METHODSThe MR scans of 14 patients with metastatic adenocarcinoma to the brain were reviewed retrospectively. The signal intensity on T2-weighted scans of the solid enhancing portion of the tumors was compared with white matter. Histologic examination of the surgical specimens included special stains to search for calcium, mucin, and iron.RESULTSEight of nine surgical and all six nonsurgical lesions were either iso- or hypointense to white matter on T2-weighted scans. There was no correlation with tumor histology or the presence of mucin, blood products, iron, or calcium.CONCLUSIONSThe presence of a hypointense intraaxial mass on T2-weighted scans strongly suggests the possibility of metastatic adenocarcinoma. The MR appearance is not explained by the presence of mucin, blood products, iron, or calcium. This phenomenon most likely reflects the relaxation parameters of the tissue from which the metastasis arose.     

Cerebrotendinous xanthomatosis: the spectrum of imaging findings and the correlation with neuropathologic findings

PURPOSE: To describe imaging findings and their neuropathologic correlate in patients with cerebrotendinous xanthomatosis (CTX). MATERIALS AND METHODS: Computed tomographic (CT) and magnetic resonance (MR) images in 24 patients with symptoms (mean age at time of imaging, 37 years; mean disease duration, 18 years) were reviewed for site and frequency of brain, spinal cord, and Achilles tendon involvement. Two patients died, and imaging findings were compared with postmortem neuropathologic findings. RESULTS: Apart from nonspecific supratentorial atrophy and deep white matter changes, more typical hyperintense lesions were seen on T2-weighted images in the dentate nucleus (in 79% of patients), globus pallidus, substantia nigra, and inferior olive and extended into adjacent white matter as disease progressed. In these locations, lipid crystal clefts and perivascular macrophages, neuronal loss, demyelination, fibrosis, and reactive astrocytosis were found at microscopic examination. Hypointensity was sometimes found on T2-weighted images in the dentate nucleus and was related to deposition of hemosiderin and calcifications. CT depicted fewer lesions; all had low attenuation, except for the calcifications. Spinal cord MR imaging revealed increased signal intensity in the lateral and dorsal columns on T2-weighted images. Achilles tendon xanthomas displayed intermediate signal intensity on T1- and T2-weighted images. CONCLUSION: The typical pattern of MR imaging findings reflects the classic histopathologic findings and should prompt the diagnosis of CTX.     

MR assessment of brain maturation: comparison of sequences.

PURPOSETo evaluate the role of short-inversion-time inversion-recovery (STIR) sequences in assessment of brain maturation.METHODSTwenty-seven infants and young children with normal neurologic development were examined by 1.5-T MR using a circularly polarized head coil. Axial T1-weighted and T2-weighted and spin-echo and STIR images were obtained. Signal intensity of different anatomic structures at individual sequences was classified relatively to reference sites and temporal sequence of signal intensity was observed.RESULTSSignal intensity changes on T1-weighted and T2-weighted spin-echo sequences occurred at ages described in various previous publications. On STIR images intensity changes became apparent at a time between T1-weighted and T2-weighted images. The advantages of the STIR sequence were improved assessment of myelination of subcortical cerebral white matter from 6 to 14 months and good contrast between white matter lesions and cerebrospinal fluid.CONCLUSIONOur results suggest that from 0 to 6 months myelination can be assessed best using a combination of T1-weighted and T2-weighted images; from 6 to 14 months a combination of T2-weighted and STIR images seems to be advantageous; after 14 months the use of only T2-weighted sequences is sufficient. After 14 months STIR images may be useful in detecting small periventricular white matter lesions or in cases with retarded myelination and isointensity between gray matter and white matter.     

Rathke cleft cyst: MR and biomedical analysis of cyst content

PURPOSE: At least one type of Rathke cleft cyst has unique MR findings, specifically, high intensity on T1-weighted images and iso- to low intensity on T2-weighted images relative to white matter. To clarify the influence of cyst content on MR images, we analyzed the cyst content by biomedical methods after surgical removal. METHOD: We studied five patients diagnosed with Rathke cleft cyst, whose MR images showed high intensity on T1-weighted images and iso- to low intensity on T2-weighted images. After surgery, total protein and cholesterol levels were quantified, and correlations of protein and cholesterol content with T1 and T2 signal intensities were performed in vitro. RESULTS: All five cysts had very high concentrations of protein (11,700-26,600 mg/dl, mean 17,940 mg/dl) with nearly no cholesterol (at most 2.0 mg/dl). Along with increases in protein concentration in vitro, the signal intensity of T1-weighted images increased, while that of T2-weighted images decreased. In contrast, the cholesterol concentration sequence influenced the signal intensity of neither T1- nor T2-weighted images. CONCLUSION: The unique MR finding of Rathke cleft cysts--high signal intensity on T1-weighted images and low signal intensity on T2-weighted images--might depend mainly on protein concentration, not on cholesterol.     

18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images

PURPOSE: To study brain MRI findings in patients with 18q- syndrome and to correlate these findings with the results of the molecular breakpoint analysis. MATERIALS AND METHODS: Brain MR images of 17 patients with 18q- syndrome were evaluated. Segregation analysis was performed with 15 microsatellite markers to determine the deletion breakpoints and whether the deletion included the myelin basic protein (MBP) gene. RESULTS: One patient had an interstitial deletion of 18q which spared the MBP gene. He was the only one with normal brain MRI. All 16 patients with deletions including the MBP gene had abnormal white matter in MRI. The main finding was poor differentiation of gray and white matter on T2-weighted images due to increased white matter signal intensity. In addition, measured signal intensity of the white matter was significantly increased in patients compared with controls. CONCLUSIONS: Poor differentiation of gray and white matter on T2-weighted images is the most typical MRI finding of the 18q- syndrome. These results support the postulation that abnormal myelination in 18q- syndrome is due to haploinsufficiency at or near the MBP locus.     

Osteogenic sarcoma: MR signal abnormalities of the brain in asymptomatic patients treated with high-dose methotrexate

The advent of lesions with high signal intensity in periventricular white matter was incidentally observed on T2-weighted images in one patient who underwent magnetic resonance (MR) imaging of the brain after administration of high-dose methotrexate (HDMTX) for osteogenic sarcoma. Twenty-one additional symptom-free patients who had been treated with the same regimen and 10 patients who had undergone cisplatin-based chemotherapy for testicular cancer also underwent examination. Fourteen of the patients with osteosarcoma showed high-signal-intensity lesions in white matter on T2-weighted images. The interval between the last course of chemotherapy and MR imaging was a factor in this finding, as 12 of 14 patients who underwent examination within 2 years after chemotherapy had a positive finding, as opposed to two of eight patients who underwent examination later. The patients with testicular cancer had normal MR images. The occurrence of MR imaging abnormalities in asymptomatic patients treated with HDMTX for osteogenic sarcoma may be subclinical evidence of treatment-related central nervous system toxicity.