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Nuclear magnetic resonance imaging of the brain in multiple sclerosis.

Ten patients with multiple sclerosis (MS) were scanned by means of cranial X-ray computed tomography (CT) with and without intravenous contrast enhancement, and by nuclear magnetic resonance (NMR) using an inversion-recovery sequence. Altogether 19 lesions varying in size between about 7 mm X 5 mm and 13 mm X 8 mm were demonstrated by CT. They were all situated in the periventricular region. Two patients also showed moderate ventricular enlargement. In addition to these abnormalities 112 further lesions were demonstrated on the NMR scans. These lesions varied in size from 4 mm X 3 mm to 12 mm X 7 mm and were particularly well seen in the periventricular region and brainstem. Care is required in the assessment of NMR scans to exclude artefacts, background noise, and mottle as well as normally situated grey matter and partial volume effects from cerebral sulci. NMR nevertheless demonstrates abnormalities in MS on a scale not previously seen except at necropsy.

Adolescent↗

Prognostic value of magnetic resonance imaging in monosymptomatic optic neuritis.

PURPOSE: Magnetic resonance imaging is able to depict lesions in the optic nerve in the acute stage of monosymptomatic optic neuritis. Most patients have lesions located intraorbitally, intracanalicularly, and/or intracranially. The goal of this study is to determine whether these lesions resolve after visual recovery, change in length or localization, or could be correlated to the visual function. METHODS: Between 1987 and 1992, the authors examined 22 patients with acute optic neuritis using magnetic resonance imaging short-time inversion recovery sequences. Additionally, the authors determined visual acuity, visual field, color vision, contrast sensitivity, and visual-evoked responses. All patients were re-examined between 1993 and 1994 in the same manner. Visual recovery in the re-examination was divided into three groups: group 1 with complete visual recovery (visual acuity better than 20/25); group 2 with incomplete recovery (visual acuity better than 20/25 but defect in at least one of the other tests: visual field, color vision, and contrast sensitivity); and group 3 with partial recovery (visual acuity remained less than 20/25, defect in all the other tests). RESULTS: All group 1 patients initially had lesions less than 17.5 mm, group 2 patients had lesions greater than 17.5 mm (44%) and/or lesions located intracanalicularly (66%), and most of group 3 patients initially had lesions greater than 17.5 mm (79%). CONCLUSION: Eyes with lesions less than 17.5 mm in the optic nerve in acute optic neuritis have a good prognosis for visual recovery. Lesions greater than 17.5 mm or lesions involving the intracanalicular portion of the optic nerve lead to incomplete or partial visual recovery.

Acute Disease↗

Identification and characterization of a Plasmodium falciparum RNA polymerase gene with similarity to mitochondrial RNA polymerases.

Nearly all mitochondrial RNA polymerase genes identified to date are encoded in the nucleus and have similarities to T3 and T7 bacteriophage RNA polymerases. Some chloroplast genes are also transcribed by T3/T7 phage-like RNA polymerases, raising the possibility that the apicomplexan parasites, which have both a mitochondrion and a plastid, might have two such genes. As part of an investigation of Plasmodium falciparum organelle transcription, we initiated a search for T3/T7 bacteriophage-like RNA polymerase genes. We employed degenerate primers based on highly conserved plant, animal and fungal mitochondrial RNA polymerase sequences to amplify corresponding P. falciparum sequences by polymerase chain reaction (PCR). Less well-conserved flanking sequences were obtained by inverse PCR. The resulting sequence predicts a 1503 amino acid open reading frame with similarity to other T3/T7 phage-like RNA polymerases. Essential amino acids that have been identified in T7 mutant analyses are conserved in the P. falciparum RNA polymerase gene. Comparison of the sequence with preliminary data from the P. falciparum genome sequencing project revealed strain heterogeneity within two regions of the gene. The amino-terminal predicted amino acid sequence of the RNA polymerase gene has similarities to mitochondrial targeting sequences. Taken together, these points suggest that we have identified the P. falciparum mitochondrial RNA polymerase gene.

Amino Acid Sequence↗

Relations between early prespike magnetic field changes, interictal discharges, and return to basal activity in the neocortex of rabbits.

To evaluate possible prespike field synchronizations, its relation to both interictal discharges and postspike return to baseline, penicillin-induced cortical interictal discharges were recorded in anaesthetized rabbits by magnetoencephalography (MEG) and electrocorticography (EcoG). Statistical parameters of spatial (global field power (GFP)) and temporal properties (Z-parameter) of field synchronization were calculated. In our previous report, three types of prespike field synchronization were found before the onset of interictal spike. We report here that the continuous and fluctuating, but not the abrupt prespike increases, were more often associated with a spike and wave pattern of interictal discharge than with a spike alone. Furthermore, the postspike return of these statistical parameters shows the same three patterns as the prespike field synchronizations, but in the inverse time sequence. More often than not pre- and postspike pattern were of the same type. The results suggest an influence of prespike field synchronization upon interictal discharge and subsequent field return dynamics.

Animals↗

Magnetic resonance imaging of heterotopic gray matter.

Heterotopic gray matter was detected by means of magnetic resonance imaging in a 3-year-old girl with left hemiparesis and atonic seizures. In the inversion recovery sequence, a large area of decreased signal intensity was noted in the right centrum semiovale and differentiation of the right basal ganglia was not clear. We speculated that the brain malformation in our patient occurred at ten weeks conceptional age.

Basal Ganglia↗

Echo-planar microscopy of porous rocks.

A modified version of the echo-planar imaging sequence incorporating multiple 180 degrees RF pulses (PEPI) has been implemented at 11.7 T and used to generate high resolution images of porous solids. By preceding the PEPI sequence with an inversion recovery or flow-encoding sequence, rapid T1, and velocity mapping is possible in the microscopic domain.

Echo-Planar Imaging↗

Fat suppression techniques in MRI: an update.

Due to short relaxation times, fat has a high signal on magnetic resonance images (MRI). This high signal, easily recognized on MRI, may be useful to characterize a lesion. However, small amounts of lipids are more difficult to detect on conventional MRI. In addition, the high signal due to fat may be responsible for artifacts such as ghosting and chemical shift. Lastly, a contrast enhancing tumor may be hidden by the surrounding fat. These problems have prompted development of fat suppression techniques in MRI. Fat may be suppressed on the basis of its difference in resonance frequency with water by means of frequency selective pulses or phase contrast techniques, or on the basis of its short T1 relaxation time by means of inversion recovery sequences. Lastly, hybrid techniques combining several of these fat suppression techniques are also possible. The aim of this paper is to review the basic principles of all these fat suppression techniques and to exemplify their clinical use.

Adipose Tissue↗

White matter alterations associated with chromosomal disorders.

White matter alterations in chromosomal disorders have been reported mainly in 18q-syndrome. Our aim was to evaluate white matter alterations in patients with chromosomal abnormalities detected through conventional cytogenetic techniques. Forty-four patients with chromosomal abnormalities, excluding trisomy 21, were diagnosed in our hospital between May 1999 and December 2002 (24 males, 20 females; mean age 6 years 4 months [SD 3 years 2 months], range 0 to 18 years). Of the 44 patients, 14 had brain magnetic resonance imaging (12 males, 2 females; mean age 4 years 2 months [SD 4 years 4 months]; five with sex chromosomal disorders [SCD] and nine with autosomal chromosomal disorders [ACD]). Of these 14 patients, eight (four with SCD and four with ACD) had abnormal white matter findings of similar patterns. These patients had pseudonodular, subcortical, and periventricular white matter high signal intensity images in T2, and fluid-attenuated inversion recovery sequences that were isolated or confluent. The images did not correlate with the neurological clinical state. Given that eight of the 14 patients showed these lesions, their prevalence in different chromosomal abnormalities appears to be high, even though they have not been well reported in the literature. To our knowledge, these alterations have never been described in SCD. We concluded that unknown factors related to the myelination processes may be localized in different chromosomes.

Abnormalities, Multiple↗

Hyperperfusion syndromes: insight into the pathophysiology and treatment of hypertensive encephalopathy.

Hypertensive encephalopathy is one of the manifestations of a hypertensive crisis. It is not the absolute value of the blood pressure that causes the encephalopathy, rather the presence of an abrupt rise in pressure. In terms of clinical and radiographic findings, there are many similarities among a group of entities, including hypertensive encephalopathy, eclampsia, and immunosuppressant neurotoxicity. Hyperperfusion syndromes may represent these clinical disease states that may share the same pathophysiology. Magnetic resonance imaging fluid attenuated inversion recovery sequences have recognized the prominent cortical involvement of the disease that had been previously missed on computed tomography. Studies have found cortical involvement in 94% of their patients, particularly in mild cases. Animal models demonstrate endothelial damage and enhanced pinocytosis in the cortex as reasons why edema may begin in that region of the brain. Patients diagnosed with hypertensive encephalopathy should be diagnosed and treated promptly in order to avoid further neurological complications. The mean arterial pressure should be lowered by 20% to 25% within the first hour of patient presentation, followed by further gradual reduction in blood pressure over the following 24 hours. Hypertensive emergency in acute ischemic stroke should be managed with more caution. According to the 2003 American Stroke Association treatment guidelines, for patients with ischemic stroke not eligible for thrombolytic therapy, target blood pressures are a diastolic blood pressure <120 mmHg and systolic blood pressure <220 mmHg. The systolic pressure must be <185 mmHg and diastolic pressure <110 mmHg at all times if eligible for thrombolytic therapy.

Animals↗

A cross-polarization magic-angle spinning 13C NMR characterization of the stable solid-state forms of cimetidine.

Proton decoupled, cross-polarization magic-angle spinning 13C NMR spectra of four polymorphic forms (A, B, C, and D) and a monohydrate form (M1) of the histamine H2 antagonist cimetidine were obtained, and the chemical shifts of the various forms were tabulated. A modified polarization inversion pulse sequence was used to distinguish quaternary, methine, methylene, and methyl carbon resonances and thereby assist spectral assignment. It is also shown that the solid-state form of cimetidine in a commercial formulation can be reliably ascertained by NMR, despite the presence in the spectrum of signals from organic excipients that are much more intense than those from the compound.

Carbon Isotopes↗

Electron spin-lattice relaxation studies of different forms of the S(2) state multiline EPR signal of the Photosystem II oxygen-evolving complex.

The pulsed EPR inversion recovery sequence has been utilized to monitor the temperature dependence of the electron spin-lattice relaxation rate of the Mn cluster of the Photosystem II oxygen evolving complex poised in a variety of S (2) state forms giving rise to g = 2 multiline EPR signals. A previous study (Lorigan and Britt (1994) Biochemistry 33: 12072-12076) showed that for PS II membranes treated with 5% ethanol, the S (2) state Mn cluster relaxes via the Orbach spin-lattice relaxation mechanism, where the relaxation is enhanced via phonon scattering off an excited state spin manifold, in this case at an energy of Delta = 36.5 cm(-1) above the S = 1/2 ground state giving rise to the multiline EPR signal. Parallel experiments are reported for PS II membranes with 5% methanol, treated with ammonia, and following short and long term dark adaptation. In each case, the temperature dependence of the electron spin-lattice relaxation rate is consistent with Orbach relaxation, and the range of excited state energies is relatively narrow (33.8 cm(-1) </= Delta </= 39.7 cm(-1)). In addition, short term dark adapted (6 min, 'active state') PS II membranes show biphasic recovery traces which indicate that a minority fraction of the oxygen evolving complexes are trapped in a form with greatly slowed spin-lattice relaxation.

Journal Article↗

Mapping myocardial viability using interleaved T1-T2* weighted imaging.

The present study was to evaluate the efficacy of our interleaved T1-T2* weighted imaging for assessing myocardial viability. The left anterior descending coronary artery (LAD) of pig hearts (n = 7) were occluded for 2 h, followed by 1 h reperfusion. After removed from animals, the hearts were perfused in a Langendorff apparatus with a mixture of pig blood and crystalloid solution in 1:1 ratio. T1 relaxation times of the myocardium were measured with a TurboFLASH inversion-recovery sequence. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.05 mmol/kg body wt) was then injected as a bolus into the aortic perfusion line. The first pass of the contrast agent through the heart was followed using the interleaved T1-T2* imaging sequence. Once the concentration of the contrast agent was in an equilibrium state, T1 relaxation times were measured again. It was found that the percentage recovery of T2* intensity (PRT2*) at the maximum T1 intensity measured during the first pass of the contrast agent with the interleaved T1-T2* imaging was significantly higher in infarcted myocardium than in normal myocardium. Moreover, the regions showing a high T2* percentage recovery on PRT2* maps matched well with the infarcted myocardium demarcated with triphenyl tetrazolium chloride (TTC) staining. We therefore conclude that infarcted myocardium can be delineated using the interleaved T1-T2* imaging method.

Animals↗

Magnetic resonance imaging in thyroid eye disease.

We examined 25 patients with thyroid eye disease, using both the STIR (Short Tau Inversion Recovery) sequence and cine MRI techniques. A number of characteristic features can be seen on the cine MRI. There is muscle enlargement with restriction of movement and, in the burnt-out phase of the disease, reduced elasticity of the muscles is manifest as their failure to stretch on eye movement. This is in contrast to the active phase of the disease, where although the muscles are enlarged, muscle stretching is clearly visible. The STIR sequence gives an assessment of muscle water content, and hence a high signal is seen in active disease. Combining these techniques is useful in assessing the level of disease activity in thyroid eye disease, and helps in planning further management.

Disease Progression↗

Evidence from the AD 2000 Izu islands earthquake swarm that stressing rate governs seismicity.

Magma intrusions and eruptions commonly produce abrupt changes in seismicity far from magma conduits that cannot be associated with the diffusion of pore fluids or heat. Such 'swarm' seismicity also migrates with time, and often exhibits a 'dog-bone'-shaped distribution. The largest earthquakes in swarms produce aftershocks that obey an Omori-type (exponential) temporal decay, but the duration of the aftershock sequences is drastically reduced, relative to normal earthquake activity. Here we use one of the most energetic swarms ever recorded to study the dependence of these properties on the stress imparted by a magma intrusion. A 1,000-fold increase in seismicity rate and a 1,000-fold decrease in aftershock duration occurred during the two-month-long dyke intrusion. We find that the seismicity rate is proportional to the calculated stressing rate, and that the duration of aftershock sequences is inversely proportional to the stressing rate. This behaviour is in accord with a laboratory-based rate/state constitutive law, suggesting an explanation for the occurrence of earthquake swarms. Any sustained increase in stressing rate--whether due to an intrusion, extrusion or creep event--should produce such seismological behaviour.

Journal Article↗

Prevalence of BRCA1/2 variants in an Ovarian Cancer Cohort: outcomes from a Nationwide Testing Program.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the management of BRCA1- and BRCA2-associated ovarian cancer (OC). In 2020, Ireland implemented a nationwide, oncology-led pathway for mainstreamed BRCA1/2 testing in patients with OC. This study evaluated the pathway and characterised the BRCA1/2 landscape in an Irish cohort of patients with OC. Samples collected between January 2020 and December 2023 were tested in two national molecular diagnostic laboratories. Single-molecule molecular inversion probe sequencing was used to detect single nucleotide variants, while multiplex ligation-dependent probe amplification assessed large genomic rearrangements. Variants were classified according to the American College of Medical Genetics and Genomics and Association for Clinical Genomic Science 2020 guidelines and CanVIG-UK specifications. In total, 535 patients were included, with a median age of 65.5 years (range, 27-89 years). Of these, 455/535 (85.0%) underwent germline BRCA1/2 (gBRCA) testing using peripheral blood, and 360/535 (67.2%) underwent tumour BRCA1/2 (tBRCA) testing, resulting in 292/535 (54.6%) patients having paired testing. Among gBRCA-tested patients, 10.3% (47/455) had a clinically actionable variant (CAV), while 2.1% (10/455) had a variant of uncertain significance. Of the 262 patients who underwent paired testing and had negative gBRCA results, 9.5% (25/262) had a somatic BRCA CAV. Recurrent germline BRCA CAVs were identified in regional clusters, including BRCA1 c.5266dup, BRCA1 c.1175_1214del, and BRCA2 c.4398_4402del. This nationwide real-world study demonstrates that mainstreamed germline and somatic BRCA1/2 testing is feasible in Ireland and reports the prevalence of BRCA CAVs in a cohort of patients with OC. Although the observed prevalence of germline BRCA CAVs was lower than anticipated, it is consistent with UK real-world data. The identification of recurrent, regionally clustered germline variants further enhances the characterisation of the Irish genomic landscape.

Journal Article↗

Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation.

Neurotoxicity is a significant complication of the use of tacrolimus. From April 1998 to December 2001, we identified 10 patients (six women, four men) who developed 11 episodes of tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) after allogeneic haematopoietic stem cell transplantation for haematological malignancies. The diagnosis was made by characteristic clinical findings (mental status changes, seizures, neurological deficits) with the exclusion of other causes and characteristic imaging findings. The median age was 35.5 years (range 19-57 years). Seven patients received a matched-unrelated donor transplant and three received a cord blood transplant. The overall incidence of PRES was 1.6%, while the incidence in matched-unrelated, mismatched-related and cord blood transplants was 3.5%, 4.9% and 7.1% respectively. Mental status changes, cognitive deficits, seizures and lethargy were the most common clinical findings. Eight of 10 patients had characteristic findings of hyperintensity of the white matter on T2-weighted images and FLAIR (fluid-attenuated inversion recovery) sequence on magnetic resonance imaging of the brain. Serum tacrolimus levels were within the therapeutic range in most patients. Tacrolimus treatment was continued (n = 4) or temporarily withheld (n = 7) for 1-14 d. One patient was changed to cyclosporine. In most patients, subsequent treatment with tacrolimus was well tolerated without recurrence of neurotoxicity.

Adult↗

[MRI follow-up study of aseptic osteonecrosis (AON) in children treated with chemotherapy for malignant diseases].

PURPOSE: The aim of the study was to evaluate by MRI the course of aseptic osteonecrosis (AON) after chemotherapy in children with different malignancies. MATERIAL AND METHODS: Retrospective analysis of 72 MRI studies in 20 children (age: 3.2-18.4 years) presenting with AON after chemotherapy. 8 children were treated exclusively with relief of weightbearing structures, whereas 12 children were additionally treated with hyperbaric oxygen therapy (HBO). Within a range of 3-76 months each patient received 1-6 follow-up exams. The acquired series included multi planar spin-echo as well as fatt-suppressed inversion recovery sequences. The MRI examinations were evaluated by a point-score system (1-6) by two radiologists. RESULTS: AON was most commonly seen in the pedal bones (26.4%), in the hip (23.6%), and in the knee joints (19.4%). Initial findings revealed an average score of 3.1 points. Based upon these initial findings, subsequent analyses show a statistically significant (p < 0.05) score increase of 0.6 score-points. For the observed intervals a: < 6 months, b: 6-12 months, and c: > 12 months the mean scores were: a: 3.3, b: 3.7, and c: 4.5 points. During the observed time period 5 patients were surgically treated in the affected bone areas. CONCLUSION: The majority of chemotherapy associated AON which initially present with advanced findings showed in MRI a progression with frequent destruction of the joint surface over their further course. More discrete forms of AON, especially osteoedema, can be positively influenced by conservative therapy.

Adolescent↗

Subcortical laminar heterotopia in two sisters and their mother: MRI, clinical findings and pathogenesis.

MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was considered most useful in the demonstration of the heterotopic band of gray matter and the assessment of cortical thickness. The younger sister presented with epileptic seizures at the age of five months and a delayed achievement of developmental milestones. The older sister of seven years had epileptic seizures since the age of one year, and developmental delay. Their mother has only had one seizure-like episode at the age of 39. Her psychomotor development had been normal. Investigation of DNA samples of the three female family-members revealed a mutation in the X-linked doublecortin gene. Within families with band heterotopia, this gene has also been related to male family members with lissencephaly.

Adult↗