Diffusion imaging in neurological disease.

Diffusion-weighted imaging can be used to assess the microscopic properties of measured tissues, providing insights into the architecture of neural tissues and how they change in physiological and pathological states. Such imaging data can be readily quantified to provide numerical values of parameters that have clinical relevance, particularly in regard to cellular constituents of tumours, chemical contents of cysts, the integrity of neuronal cell bodies and myelin sheaths. Diffusion based techniques have proven to be particularly useful in investigating cerebral infarction, cerebral infections, epidermoid and other cysts, cerebral tumours, and white matter disorders. The purpose of this review is to introduce key concepts in diffusion imaging and illustrate how it may be applied to clinical practice, with particular reference to head injury.

Comparing the accuracy of initial head CT reporting by radiologists, radiology trainees, neuroradiographers and emergency doctors.

OBJECTIVES: Demand for out-of-hours cranial CT imaging is increasing and some departments have considered addressing this shortfall by allowing non-radiologists to provisionally report imaging studies. The aim of this work was to assess whether it is appropriate for non-radiologists to report head CTs by comparing the misreporting rates of those who regularly report head CTs with two groups of non-radiologists who do not usually report them: neuroradiographers and emergency doctors. METHODS: 62 candidates were asked to report 30 head CTs, two-thirds of which were abnormal, and the results were compared by non-parametric statistical analysis. RESULTS: There was no evidence of a difference in the score between neuroradiographers, neuroradiologists and general consultant radiologists. Neuroradiographers scored significantly higher than senior radiology trainees, and the emergency doctors scored least well. CONCLUSION: The results of this preliminary study show that appropriately trained neuroradiographers are competent at reporting the range of abnormalities assessed with this test and that their misreporting rates are similar to those who already independently report these studies.

Minimally-invasive fetal autopsy using magnetic resonance imaging and percutaneous organ biopsies: clinical value and comparison to conventional autopsy.

OBJECTIVES: Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy. METHODS: Forty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the 'gold standard'. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy. RESULTS: In 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance. CONCLUSIONS: Although in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases.

Use of a confidence scale in reporting postmortem fetal magnetic resonance imaging.

OBJECTIVES: Postmortem magnetic resonance imaging (MRI) may be an alternative to conventional autopsy. However, it is unclear how confident radiologists are in reporting such studies. We sought to determine the confidence with which radiologists report on various fetal organs by developing a scale to express their confidence of normality and abnormality, and to place this in the context of a pathological diagnosis of whether the organ was in fact normal or abnormal. METHODS: Thirty fetuses, aged 16-39 gestational weeks and weighing 61-3270 g, underwent postmortem MRI prior to conventional autopsy. MRI studies were reported by two radiologists with access to the clinical and sonographic history: a neuroradiologist, reporting head and neck, and a pediatric radiologist, reporting thorax, abdomen and pelvis. Radiologists used a scale (0 = definitely abnormal, 100 = definitely normal, 50 = unable to comment) to indicate their confidence of anatomical structures being normal or abnormal, using a checklist. Conventional autopsies were performed by pediatric pathologists blinded to the MRI findings, and these were considered the reference standard. RESULTS: Most normal fetal organs had high scores on postmortem MRI, with median confidence scores above 80. However, the atrioventricular valves, duodenum, bowel rotation and pancreas proved more difficult to assess, with median scores of 50, 60, 60 and 62.5, respectively. Abnormal cardiac atria and ventricles, kidneys, cerebral hemispheres and corpus callosum were always detected with high or moderate degrees of confidence (median scores of 2.5, 5, 0, 0 and 30 respectively). However, in two cases with abnormal cardiac outflow tracts, both cases scored 50. Kappa values, assessing agreement between MRI diagnoses of abnormality and autopsy, were high for the brain (0.83), moderate for the lungs (0.56) and fair for the heart (0.33). CONCLUSIONS: This scoring system represents an attempt to define the confidence of radiologists to report varying degrees of normality and abnormality following z ex-utero fetal MRI. While most fetal anatomy is clearly visualized on postmortem MRI, radiologists may lack confidence reporting such studies and there are particular problems with assessment of some cardiac and gastrointestinal structures, both normal and abnormal.

Reproducibility of volume measurements of vestibular schwannomas - a preliminary study.

OBJECTIVE: A preliminary study to investigate the intra-observer and inter-observer variability of measurements of vestibular schwannoma volume using an area-tracing and linear dimension measurement method. DESIGN: Prospective blinded measurements by two observers (one a consultant and one a sub-specialty trainee in neuroradiology). SETTING: Ambulatory patients with known vestibular schwannoma attending a tertiary referral centre. PARTICIPANTS: Twenty-three patients with 26 vestibular schwannomas aged 29-80 years old. MAIN OUTCOME MEASURE: Quantification of the variability in measured volume due to intra- and inter-observer measurement differences, expressed as reliability coefficients within which 95% of repeated measurements are calculated to lie from each other in relative percentage terms. RESULTS: For the linear measurement method, intraobserver variability was calculated to have a reliability coefficient of 65% and for interobserver variability this was 155%. For the area tracing method, the corresponding coefficients were 26% for intraobserver variability and 44% for interobserver variability. CONCLUSIONS: Volume measurements in vestibular schwannoma are variable even when the measurements are made by the same observer on identical images. The area tracing method, commonly regarded as the gold standard, is less variable than a linear method but still introduces more variability than commonly realized (for 95% of patients, repeated measurements by the same observer lie within around 25% of each other). Manual area tracing is not widely used in practice because it is time consuming and reliable automated methods are eagerly awaited.

Detection and evaluation of intracranial aneurysms with 16-row multislice CT angiography.

AIM: The aim of this study was to assess the usefulness of 16-row multislice CT angiography (CTA) in evaluating intracranial aneurysms, by comparison with conventional digital subtraction angiography (DSA) and intraoperative findings. METHODS: A consecutive series of 57 patients, scheduled for DSA for suspected intracranial aneurysm, was prospectively recruited to have CTA. This was performed with a 16-detector row machine, detector interval 0.75 mm, 0.5 rotation/s, table speed 10mm/rotation and reconstruction interval 0.40 mm. CTA studies were independently and randomly assessed by two neuroradiologists and a vascular neurosurgeon blinded to the DSA and surgical findings. Review of CTA was performed on workstations with an interactive 3D volume-rendered algorithm. RESULTS: DSA or intraoperative findings or both confirmed 53 aneurysms in 44 patients. For both independent readers, sensitivity and specificity per aneurysm of DSA were 96.2% and 100%, respectively. Sensitivity and specificity of CTA were also 96.2% and 100%, respectively. Mean diameter of aneurysms was 6.3mm (range 1.9 to 28.1 mm, SD 5.2 mm). For aneurysms of less than 3 mm, CTA had a sensitivity of 91.7% for each reader. Although the neurosurgeon would have been happy to proceed to surgery on the basis of CTA alone in all cases, he judged that DSA might have provided helpful additional anatomical information in 5 patients. CONCLUSION: The diagnostic accuracy of 16-slice CTA is promising and appears equivalent to that of DSA for detection and evaluation of intracranial aneurysms. A strategy of using CTA as the primary imaging method, with DSA reserved for cases of uncertainty, appears to be practical and safe.

Contrast-enhanced MR angiography for carotid disease: diagnostic and potential clinical impact.

OBJECTIVE: To compare contrast-enhanced MR angiography (CEMRA) with intra-arterial digital subtraction angiography (DSA) for evaluating carotid stenosis. METHODS: A total of 167 consecutive symptomatic patients, scheduled for DSA following screening duplex ultrasound (DUS), were prospectively recruited to have CEMRA. Three independent readers reported on each examination in a blinded and random manner. Agreement was assessed using the Bland-Altman method. Diagnostic and potential clinical impact of CEMRA was evaluated, singly and in combination with DUS. RESULTS: CEMRA tended to overestimate stenosis by a mean bias ranging from 2.4 to 3.8%. A significant part of the disagreement between CEMRA and DSA was directly caused by interobserver variability. For detection of severe stenosis, CEMRA alone had a sensitivity of 93.0% and specificity of 80.6%, with a diagnostic misclassification rate of 15.0% (n = 30). More importantly, clinical decision-making would, however, have been potentially altered only in 6.0% of cases (n = 12). The combination of concordant DUS and CEMRA reduced diagnostic misclassification rate to 10.1% (n = 19) at the expense of 47 (24.9%) discordant cases needing to proceed to DSA. An intermediate approach of selective DUS review resulted in a marginally worse diagnostic misclassification rate of 11.6% (n = 22) but with only 6.8% of discordant cases (n = 13). CONCLUSIONS: DSA remains the gold standard for carotid imaging. The clinical misclassification rate with CEMRA, however, is acceptably low to support its safe use instead of DSA. The appropriateness of combination strategies depends on institutional choice and cost-effectiveness issues.

Prevalence of cystic paraurethral structures in asymptomatic women at endovaginal and perineal sonography.

AIM: To prospectively assess the prevalence of paraurethral cystic structures in asymptomatic adult women. PATIENTS AND METHODS: One hundred and forty consecutive women undergoing endovaginal sonography with no history of lower urinary tract symptoms. RESULTS: Paraurethral cystic structures were identified in 4/140 subjects (2.9%). Ultrasound assessment allowed rapid definition of the site, size and vascularity of these lesions and was well tolerated by the patient. CONCLUSION: This is the first prospective ultrasound study to determine the prevalence of paraurethral cystic structures in a large consecutive cohort of asymptomatic women. Our findings are in accordance with previously published post-mortem data and surgical series which have estimated the prevalence of paraurethral cystic structures to be between 1 and 6%.

Imaging of compressive vertebral haemangiomas.

Compressive vertebral haemangiomas (VHs) are rare. Correct preoperative diagnosis is useful both for operative planning (since compressive VHs are extremely vascular lesions) and to allow preoperative embolisation. Numerous radiological signs for VHs have been described, but compressive VHs frequently have atypical features. In particular, magnetic resonance features are not well established. We present imaging features in three cases of compressive VH and review the imaging findings in an additional 106 previously published cases. Findings were typical in 52 of 80 plain film (65%), 33 of 41 computed tomography (80%) and 13 of 25 magnetic resonance examinations (52%). The prevalence of previously described imaging features is reported. Awareness of the range of magnetic resonance features is important since this is frequently the initial investigation in patients presenting with symptoms of neural compression. Since computed tomography is typical in 80% of cases, this is a useful confirmatory test if magnetic resonance features are suspicious but not diagnostic of compressive VH.

Value of computed tomography and magnetic resonance imaging in the treatment of a calcifying epithelial odontogenic (Pindborg) tumour.

The calcifying epithelial odontogenic (Pindborg) tumour is a rare primary tumour of the jaw with a characteristic histological appearance. We describe here its appearance on computed tomography (an expanding, multilocular lesion that is thinning both plates of the mandible, is well-defined and contains scattered radio-opaque areas) and magnetic resonance imaging (predominantly hypointense on T1-weighted images and of mixed hyperintensity on T2-weighted images; the extent of the tumour including involvement of the mandibular canal was clear).

Specific patterns of cognitive impairment in patients with idiopathic normal pressure hydrocephalus and Alzheimer's disease: a pilot study.

OBJECTIVES: Eleven patients with idiopathic normal pressure hydrocephalus (NPH) were selected from an initial cohort of 43 patients. The patients with NPH fell into two distinctive subgroups: preshunt, group 1 (n=5) scored less than 24 on the mini mental state examination (MMSE) and were classified as demented and group 2 (n=6) scored 24 or above on the MMSE and were classified as non-demented. METHODS: All patients were neuropsychologically assessed on two occasions: preshunt and then again 6 months postshunt. Group 1 completed the mini mental state examination (MMSE) and the Kendrick object learning test (KOLT). In addition to the MMSE and KOLT, group 2 completed further tasks including verbal fluency and memory and attentional tasks from the CANTAB battery. Nine of the 11 patients also underwent postshunt MRI. RESULTS: Group 1, who, preshunt, performed in the dementing range on both the MMSE and KOLT, showed a significant postoperative recovery, with all patients now scoring within the normal non-demented range. Group 2, although showing no signs of dementia according to the MMSE and KOLT either preshunt or postshunt, did show a specific pattern of impairment on tests sensitive to frontostriatal dysfunction compared with healthy volunteers, and this pattern remained postoperatively. Importantly, this pattern is distinct from that exhibited by patients with mild Alzheimer's disease. Eight of the nine patterns of structural damage corresponded well to cognitive performance. CONCLUSIONS: These findings are useful for three main reasons: (1) they detail the structural and functional profile of impairment seen in NPH, (2) they demonstrate the heterogeneity found in this population and show how severity of initial cognitive impairment can affect outcome postshunt, and (3) they may inform and provide a means of monitoring the cognitive outcome of new procedures in shunt surgery.

Differential expression of stress proteins in nonhuman primate lung and conducting airway after ozone exposure.

The presence of seven stress proteins including various heat shock proteins [27-kDa (HSP27), 60-kDa (HSP60), 70-kDa (HSP70) and its constitutive form HSC70, and 90-kDa (HSP90) HSPs] and two glucose-regulated proteins [75-kDa (GRP75) and 78-kDa (GRP78) GRPs] in ozone-exposed lungs of nonhuman primates and in cultured tracheobronchial epithelial cells was examined immunohistochemically by various monoclonal antibodies. Heat treatment (42 degrees C) resulted in increased HSP70, HSP60, and HSP27 and slightly increased HSC70 and GRP75 but no increase in GRP78 in primary cultures of monkey tracheobronchial epithelial cells. Ozone exposure did not elevate the expression of these HSPs and GRPs. All of these HSPs including HSP90, which was undetectable in vitro, were suppressed in vivo in monkey respiratory epithelial cells after ozone exposure. Both GRP75 and GRP78 were very low in control cells, and ozone exposure in vivo significantly elevated these proteins. These results suggest that the stress mechanism exerted on pulmonary epithelial cells by ozone is quite different from that induced by heat. Furthermore, differences between in vitro and in vivo with regard to activation of HSPs and GRPs suggest a secondary mechanism in vivo, perhaps related to inflammatory response after ozone exposure.

Scrotal trauma: a cause of testicular atrophy.

Scrotal trauma is often mentioned as a cause of testicular atrophy yet there have been few studies documenting the effect of scrotal trauma on testicular size months or years following injury. We performed clinical and sonographic examinations in 10 patients who had suffered blunt scrotal trauma. A significant reduction in volume of the injured testis was observed in 5/10 cases at follow-up sonography. In two cases the affected testis was heterogeneous and colour flow Doppler examination showed reduced flow. In three cases the testis was homogeneous but reduced in volume and in the remaining five cases the affected testis appeared normal. We conclude that testicular atrophy is a sequel of scrotal trauma and occurred in 50% of patients in this study.

Structural features of a peptide corresponding to human kappa-casein residues 84-101 by 1H-nuclear magnetic resonance spectroscopy.

The peptide Val-Arg-Arg-Pro-Asn-Leu-His-Pro-Ser-Phe-Ile-Ala-Ile-Pro-Pro- Lys-Lys-Ile, which corresponds to residues 84-101 of human kappa-casein, has been synthesized and its conformation preferences determined by 1H-nuclear magnetic resonance spectroscopy in dimethyl sulphoxide. The peptide adopted a largely extended chain conformation in solution and there was evidence for the presence of a beta-turn involving residues Pro87-His90 of human kappa-casein. The presence of a turn in this position would make the physiologically significant Arg85 residue of human kappa-casein (which is equivalent to Arg97 in bovine kappa-casein) unavailable for interaction with Asp249 of bovine chymosin, and may partly explain why human kappa-casein is hydrolysed more slowly than its bovine counterpart by bovine chymosin.

A randomized trial of spiral CT and ventilation perfusion scintigraphy for the diagnosis of pulmonary embolism.

PURPOSE: To compare spiral computed tomographic pulmonary angiography (SCTA) with lung ventilation-perfusion scintigraphy (VQS) as the initial investigation of patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS: Prospective randomized trial of 78 patients with suspected pulmonary embolism. Patients underwent either SCTA or lung VQS as their initial investigation for PE. Cross-over between groups meant that 50 patients received both examinations. The clinicians' assessment of overall clinical likelihood of PE was also collected. RESULTS: (1) It was possible to make a confident diagnosis in a significantly larger proportion of patients when SCTA was used as the initial investigation (35/39, 90%) compared with using VQS first (21/39, 54% P<0.001). The main difference between the two groups was that SCTA demonstrated lesions other than pulmonary embolism considered responsible for the patients' symptoms in 13/39 patients (33%) randomized to SCTA as the initial investigation and following a non-diagnostic VQS in 10/39 patients (25%) randomized to VQS as the initial investigation. (2) There was no difference in the prevalence or detection of PE in the two groups. SCTA demonstrated pulmonary emboli in 6/39 patients (16%) in the SCTA first group and VQS was high probability for PE in 5/39 patients (13%) in the VQS first group. SCTA detected PE in a further two patients in the VQS first group. CONCLUSION: It is proposed that, where logistically feasible, SCTA should replace VQS as the initial investigation for PE in patients with an underlying cardio-respiratory disorder.

Solution conformation of a peptide corresponding to bovine kappa-casein B residues 130-153 by circular dichroism spectroscopy and 1H-nuclear magnetic resonance spectroscopy.

The peptide Pro130-Thr-Ser-Thr-Pro-Thr-Ile-Glu-Ala-Val-Glu140- Ser-Thr-Val-Ala-Thr-Leu-GLu-Ala-Ser-Pro150-Glu-Val-Ile, which corresponds to residues 130-150 of kappa-casein B, was synthesized and the conformation of the peptide in solution investigated by circular dichroism (CD) spectroscopy, structure prediction algorithms and 1H-nuclear magnetic resonance spectroscopy. In a solution containing the structure-enhancing solvent trifluoroethanol the CD spectrum was typical of a peptide in the alpha-helical conformation and nuclear magnetic resonance showed that the amino acids between Ile136 and Ser149 (kappa-casein numbering) were predominantly in the alpha-helical conformation but that Pro130 to Thr135 and Pro150 to Ile153 were not. In addition, Thr133-Pro134 and Ser-149-Pro150 were primarily in the trans conformation, the residues from Thr131 to Thr135 were in unordered structures and the residues from Glu151 to Ile153 were in an extended conformation. Residues Glu137 to Glu140 and Thr145 to Ala148 also displayed some 3(10)-helix character. When the peptide was dissolved in 10 mM-cetyltrimethylammonium chloride solution at pH 6, the CD spectra indicated that the proportion of helical structure was comparable to that of the peptide in trifluoroethanol solution (400 ml/l), whereas when the peptide was dissolved in buffer alone in 10 mM-SDS solution, the CD spectra were consistent with a low helical content. Acidification of these solutions to pH 2.85 resulted in a slight increase in the helical content of the peptide in buffer and more markedly in buffer containing SDS. When the peptide was in 5 mM-CaCl2 solution at neutral pH, the CD spectrum indicated that some ordered structure was present. Taken together these results indicate that the ionizable residues Glu137, Glu140, Glu147 and Glu151 could be important in determining the stability of the putative helix. The structure predictions found that the sequence from Glu137 to Pro150 would be more likely to be in a helical than any other conformation in the intact bovine protein, but that pig, sheep and goat kappa-caseins did not give a prediction of a strongly helical region in this part of the molecule.

The Tweed philosophy: the Tweed years.

Charles H. Tweed revolutionized clinical orthodontics. His inquisitive scientific mind coupled with his outstanding clinical ability and his unselfish work ethic are legendary. He gave the orthodontic specialist diagnostic and mechanical treatment concepts that have stood the tests of both time and intense scrutiny.

Ureteric rupture in an elderly patient following minor trauma: case report.

A 75-year-old woman arrived at our hospital 2 weeks after falling from a bus. She was shown to have a ruptured left ureter. After drainage of a urine collection and decompression of her obstructed kidney she recovered. To our knowledge ureteric rupture has not before been reported as a consequence of such minor trauma.