Bilateral pulvinar signal intensity decrease on T2-weighted images in patients with aspartylglucosaminuria.

BACKGROUND: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal disease caused by deficiency of aspartylglucosaminidase. A thalamic T2 signal intensity decrease is associated with lysosomal diseases. PURPOSE: To investigate thalamic signal intensity in AGU by performing a retrospective review of brain magnetic resonance (MR) imaging studies of AGU patients. MATERIAL AND METHODS: A total of 25 MR examinations were available for 11 patients aged between 3 and 32 years (four patients underwent bone marrow transplantation). Of these, 13 examinations were performed after bone marrow transplantation. Five patients had from two to six examinations, and six patients had one examination each. In every patient, the diagnosis of AGU was confirmed by blood and urine tests. Eighteen examinations were performed with a 1.0T imager including dual spin-echo T2 and proton density (PD) axial and coronal images, and 10 examinations also included T1-weighted images. Seven examinations were performed with a 1.5T imager including turbo spin-echo axial and coronal T2-weighted images and axial fluid-attenuated inversion recovery (FLAIR) images; three examinations included T1-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (3D MPRAGE) images. The signal intensity of the thalamus and pulvinar in every sequence was compared to that of the putamina. RESULTS: In AGU, thalamic alterations were first detectable on T2-weighted images (25 examinations in 11 patients) from the age of 3 years 6 months, showing decreased signal intensity in 21 of 24 examinations. T1-weighted images (13 examinations) showed slightly increased thalamic signal intensity in five out of seven examinations from the age of 7 years, and PD images (19 examinations) showed decreased signal intensity from the age of 16 years (three examinations). The pulvinar showed decreased signal intensity on spin-echo T2-weighted images for 14 of 18 examinations or on FLAIR sequences for seven of seven examinations from the age of 6 years and 6 months, both in patients with and without bone marrow transplantation, but no pulvinar alterations were observable on T1 and PD images. CONCLUSION: In AGU, the thalamus is affected. Pulvinar changes are visible only on T2-weighted images, and these may be the first changes reported in the group of lysosomal diseases.

Diffusion weighted magnetic resonance imaging of rat testes: a method for early detection of ischemia.

PURPOSE: We investigated the feasibility of diffusion weighted magnetic resonance imaging (MRI) for the early detection of ischemia in the testis. MATERIALS AND METHODS: Circulation to the right testis in Wistar rats was occluded by surgical ligation of the right funicle. The left side was sham operated and served as a control. The diffusion and T2-weighted MRI images of the 2 testes was performed postoperatively by a 1.5 Tesla MRI unit using a knee coil. On apparent diffusion coefficient images and T2-weighted images the region of interest values in the 2 testes were measured and statistically compared. RESULTS: At 1 hour after testicular funicle ligation the apparent diffusion coefficient was 18% lower in the ischemic than in the sham operated testis (p <0.0098). At 2 hours the difference was 20% (p <0.0017). In the signal-to-noise ratio on T2-weighted images there was no difference in the left and right testes. CONCLUSIONS: Altered diffusion occurs in an ischemic testis, which can be measured on MRI at 1.5 Tesla. Thus, diffusion-weighted MRI may be a helpful method for the differential diagnosis of acute testicular torsion.

A shielded Overhauser marker for MR tracking of interventional devices.

Improvements to an active MR tracking technique are described. Real-time position monitoring of interventional procedures can be realized by incorporating a small marker that emits an NMR signal into the tip of an interventional device, and the marker's emitted NMR signal is enhanced by use of the Overhauser phenomenon. A significant advance over prior designs has achieved by making the marker have a cylindrical shape and by confining the saturation energy to the marker's interior. The performance of the improved active marker was verified in the laboratory and in vitro. The experiments demonstrated that the marker was visible in MR images when inserted in different excised tissues, and even in air, with positive contrast and with various imaging sequences. The tissue magnetization was minimally perturbed, and the marker emitted a variable but enhanced signal in all orientations in the magnetic field. The marker can potentially be used to mark locations on the body for frameless stereotaxy or to identify inserted devices.

Low-field magnetic resonance imaging of beagle brain with a dedicated receiver coil.

A specially designed radio frequency receiver coil was used in a low-field-strength (0.1 T) magnetic resonance imager to improve the image quality of the Beagle brain. The aim was to obtain better distinction of anatomic details with a better signal-to-noise ratio in shorter imaging time. The spin-echo (TR/TE = 1200/100; TR is the repetition time and TE is the echo time in ms) brain images of three Beagles indicate that the new receiver coil can fulfill these goals.

High-accuracy MR tracking of interventional devices: the Overhauser marker enhancement (OMEN) technique.

A new technique for visualization of interventional devices in magnetic resonance imaging is presented. Determination of the position of an invasive device is made possible by incorporating into the device a small marker that emits the NMR signal. This signal is enhanced by the use of the Overhauser phenomenon. This technique differs from the earlier reported techniques for marking interventional instruments in the sense that the contrast between the marker and tissue is not based on different relaxation rates, but on NMR signal enhancement. A prototype marker was constructed and inserted into an inductively fed loop-gap resonator that couples saturation energy with the marker. Circuit analogies are presented that model the Overhauser phenomenon and the coupling circuit. In vitro experiments demonstrated that the marker is visible in MR images up to a slice thickness of 50 mm when inserted in excised animal liver and fat tissues.

Monitoring the CNS pathology in aspartylglucosaminuria mice.

Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients.

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.

Interventional MR imaging. Demonstration of the feasibility of the Overhauser marker enhancement (OMEN) technique.

PURPOSE: The poor localization facility of interventional instruments in MR imaging has been one of the major obstacles to the popularization of interventional MR imaging. It has been suggested that the Overhauser enhancement be used to generate markers of small size and high visibility. This article studies the feasibility of a localization marker based on this method. MATERIAL AND METHODS: A small Overhauser marker was constructed on the tip of a coaxial cable and comparative images were taken by a 0.23 T imager with and without electron spin irradiation. RESULTS: During irradiation an enhanced signal intensity from the marker was observed. The signal from the marker also exceeded the signal from a 0.25 mmol MnCl2 reference phantom. CONCLUSION: Its small size and high signal-to-noise ratio, together with immunity to most system nonlinearities and imaging errors, makes the Overhauser marker a promising localization method for the accurate positioning of interventional devices. The method may be applied at any field strength, and markers are visible in images obtained with any practical imaging sequence.