In and around the pineal gland: a neuroimaging review.

Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

Use of optical coherence tomography for the diagnosis of preclinical lesions of circumscribed palmar hypokeratosis.

Circumscribed hypokeratosis of palms and soles is a rare dermatosis, usually affecting women. Diagnosis is mainly based on the clinical characteristics, including the clinical appearance and anatomical site of the skin lesions and on the demographic features of the affected patients, usually middle-aged to elderly women. Skin biopsy may be performed to confirm clinical diagnosis. Optical coherence tomography (OCT) is a technique that has been undergone substantial development in dermatology in recent years, and its use in clinical practice has been growing progressively. Several dermatological conditions have been studied with this tool, but to our knowledge, it has not been used to investigate this form of hypokeratosis. We report a case of circumscribed palmar hypokeratosis for which diagnosis was confirmed by OCT, which was performed as the patient was reluctant to undergo skin biopsy because of its invasiveness. We highlight the potential use of OCT in obtaining a virtual skin biopsy to confirm clinical diagnosis and identify preclinical skin lesions amenable to early treatment.

Lifelong physical activity in maintaining bone strength in older men and women of the Age, Gene/Environment Susceptibility-Reykjavik Study.

UNLABELLED: We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health later in life. INTRODUCTION: Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (≥65 years). METHODS: We examined if lifelong physical activity is important for maintaining bone strength in the elderly. RESULTS: The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. CONCLUSION: Our findings conclude that lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health in the elderly.

Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury.

Historically, the blood-brain barrier (BBB) was considered to be at the level of cerebral endothelium. Currently, the interaction of endothelium with other components of the vessel wall and with neurones and glial cells is considered to constitute a functional unit, termed the neurovascular unit that maintains cerebral homeostasis in steady states and brain injury. The emphasis of this review is on cerebral endothelium, the best-studied component of the neurovascular unit, and its permeability mechanisms in health and acute brain injury. Major advances have been made in unravelling the molecular structure of caveolae and tight junctions, both of which are components of the structural barrier to the entry of plasma proteins into brain. Time course studies suggest that caveolar changes precede junctional changes in acute brain injury. Additional factors modulating BBB permeability in acute brain injury are matrix metalloproteinases-2 and 9 and angiogenic factors, the most notable being vascular endothelial growth factor-A and angiopoietins (Ang) 1 and 2. Vascular endothelial growth factor-A and Ang2 have emerged as potent inducers of BBB breakdown while Ang1 is a potent anti-leakage factor. These factors have the potential to modulate permeability in acute brain injury and this is an area of ongoing research. Overall, a combination of haemodynamic, structural and molecular alterations affecting brain endothelium results in BBB breakdown in acute brain injury.

A Deep Learning-Based Approach to Reduce Rescan and Recall Rates in Clinical MRI Examinations.

BACKGROUND AND PURPOSE: MR imaging rescans and recalls can create large hospital revenue loss. The purpose of this study was to develop a fast, automated method for assessing rescan need in motion-corrupted brain series. MATERIALS AND METHODS: A deep learning-based approach was developed, outputting a probability for a series to be clinically useful. Comparison of this per-series probability with a threshold, which can depend on scan indication and reading radiologist, determines whether a series needs to be rescanned. The deep learning classification performance was compared with that of 4 technologists and 5 radiologists in 49 test series with low and moderate motion artifacts. These series were assumed to be scanned for 2 scan indications: screening for multiple sclerosis and stroke. RESULTS: The image-quality rating was found to be scan indication- and reading radiologist-dependent. Of the 49 test datasets, technologists created a mean ratio of rescans/recalls of (4.7 ± 5.1)/(9.5 ± 6.8) for MS and (8.6 ± 7.7)/(1.6 ± 1.9) for stroke. With thresholds adapted for scan indication and reading radiologist, deep learning created a rescan/recall ratio of (7.3 ± 2.2)/(3.2 ± 2.5) for MS, and (3.6 ± 1.5)/(2.8 ± 1.6) for stroke. Due to the large variability in the technologists' assessments, it was only the decrease in the recall rate for MS, for which the deep learning algorithm was trained, that was statistically significant (P = .03). CONCLUSIONS: Fast, automated deep learning-based image-quality rating can decrease rescan and recall rates, while rendering them technologist-independent. It was estimated that decreasing rescans and recalls from the technologists' values to the values of deep learning could save hospitals $24,000/scanner/year.

Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy.

Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g(-1) or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies.

Neutron stimulated emission computed tomography: a Monte Carlo simulation approach.

A Monte Carlo simulation has been developed for neutron stimulated emission computed tomography (NSECT) using the GEANT4 toolkit. NSECT is a new approach to biomedical imaging that allows spectral analysis of the elements present within the sample. In NSECT, a beam of high-energy neutrons interrogates a sample and the nuclei in the sample are stimulated to an excited state by inelastic scattering of the neutrons. The characteristic gammas emitted by the excited nuclei are captured in a spectrometer to form multi-energy spectra. Currently, a tomographic image is formed using a collimated neutron beam to define the line integral paths for the tomographic projections. These projection data are reconstructed to form a representation of the distribution of individual elements in the sample. To facilitate the development of this technique, a Monte Carlo simulation model has been constructed from the GEANT4 toolkit. This simulation includes modeling of the neutron beam source and collimation, the samples, the neutron interactions within the samples, the emission of characteristic gammas, and the detection of these gammas in a Germanium crystal. In addition, the model allows the absorbed radiation dose to be calculated for internal components of the sample. NSECT presents challenges not typically addressed in Monte Carlo modeling of high-energy physics applications. In order to address issues critical to the clinical development of NSECT, this paper will describe the GEANT4 simulation environment and three separate simulations performed to accomplish three specific aims. First, comparison of a simulation to a tomographic experiment will verify the accuracy of both the gamma energy spectra produced and the positioning of the beam relative to the sample. Second, parametric analysis of simulations performed with different user-defined variables will determine the best way to effectively model low energy neutrons in tissue, which is a concern with the high hydrogen content in biological tissue. Third, determination of the energy absorbed in tissue during neutron interrogation in order to estimate the dose. Results from these three simulation experiments demonstrate that GEANT4 is an effective simulation platform that can be used to facilitate the future development and optimization of NSECT.

Cost-effectiveness of alternative methods for diabetic retinopathy screening.

OBJECTIVE: To assess from the perspectives of a government delivery system and patients, the cost-effectiveness of the 45-degrees retinal camera compared to the standard ophthalmologist's exam and an ophthalmic exam by a physician's assistant or nurse practitioner technician, for detecting nonproliferative and proliferative diabetic retinopathy. RESEARCH DESIGN AND METHODS: Comparison of 45-degrees fundus photographs with and without pharmacological pupil dilation taken by technicians and interpreted by experts, direct and indirect ophthalmoscopy by ophthalmologists, and direct ophthalmoscopy by technicians with seven-field stereoscopic fundus photography (reference standard). Costs were estimated from market prices and actual resource use. The study included 352 patients attending outpatient diabetes and general-medicine clinics at VA and DOD facilities. RESULTS: Medical system costs per true positive were: 45-degrees photos with dilation, $295; 45-degrees photos without dilation, $378; ophthalmologist, $390; and technician, $794. Patient costs per true positive were: 45-degrees photos with dilation, $139; 45-degrees photos without dilation, $171; ophthalmologist, $306; and technician, $1009. Cost-effectiveness is sensitive to program size due to high fixed cost of the camera methods but not to prevalence. Cost-effectiveness of the technician exam is strongly affected by its sensitivity. CONCLUSIONS: Primary-care screening with retinal photographs through pharmacologically dilated pupils for diabetic retinopathy is an appropriate and cost-effective alternative to screening by an ophthalmologist in this setting. Ophthalmologists are scarce, primary-care physicians are extremely busy, and large clinics allow fixed equipment costs to be spread across many patients.

Screening for diabetic retinopathy. The wide-angle retinal camera.

OBJECTIVE: To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45 degrees retinal photograph without pharmacological dilation, and a set of three dilated 45 degrees retinal photographs) were compared with a reference standard of stereoscopic 30 degrees retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS: The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS: Fundus photographs taken by the 45 degrees camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45 degrees camera.

Functional decline in Parkinson disease.

OBJECTIVES: To determine the overall rate of functional decline and to assess the progression of different signs of Parkinson disease (PD). PATIENTS AND METHODS: Patients with clinically diagnosed PD followed up for at least 3 years were included in this study. Demographic and clinical data (including the Unified Parkinson's Disease Rating Scale [UPDRS]) were analyzed by the multivariate unbalanced repeated-measurements design using the mixed-effects model to study the association between different symptoms and various demographic variables. Regression models helped estimate the rates of progression of the disease in relationship to the various components of the UPDRS. Patients were categorized as having tremor-dominant or postural instability-gait difficulty-dominant PD and the 2 categories were compared for progression of their total UPDRS scores. DESIGN: A multivariate mixed-effects model was used to study the relationship between the different symptoms and various demographic variables. Nonparametric statistical tests were used to compare the progression of symptoms in the "on" (good function) state and the "off" (poor function) state groups for 2 age-at-onset categories (< or =57 and >57 years). RESULTS: Data from 1731 visits on 297 patients (181 men) followed up for an average of 6.36 years (range, 3-17 years) were analyzed. The annual rate of decline in the total UPDRS scores was 1.34 when assessed during the on state and 1.58 when assessed during the off state. Patients with an older age at onset had more rapid progression of PD than those with a younger age at onset. Furthermore, the older-onset group had statistically significantly more progression in mentation, freezing, and parts I (mentation) and II (activities of daily living) UPDRS subscores. Handwriting was the only component of the UPDRS score that did not notably deteriorate during the observation period. Regression analysis of 108 patients whose symptoms were rated during their off state showed a faster rate of cognitive decline as age at onset increased. The slopes (ie, the annual rates of decline) of progression in the UPDRS scores, when adjusted for age at the initial visit, were steeper for the postural instability--gait difficulty--dominant group compared with the tremor-dominant group. CONCLUSION: Based on longitudinal follow-up data, our findings provide evidence for a variable course of progression of the different PD symptoms, thus implying different biochemical or degenerative mechanisms for the various clinical features associated with PD.

Prevalence of bone demineralization in the United States.

A study of the distribution and prevalence of bone demineralization in the US population is reported. Based on the HANES I Survey data that incorporated bone density examination of V-2 by the Goldsmith and Vose techniques in a national sample of 6030 adults, it was observed that (1) age-adjusted bone density differences between sexes were consistently found when controlling for race (the prevalence of low bone density was greater among females than males) and (2) whites of both sexes had higher prevalence of low density than blacks in most age-sex categories.

Familial herpes simplex infection associated with activation of the complement system.

A patient with severe recurrent herpes infection was evaluated for immunologic analysis including a profile of complement components. The peripheral blood lymphocytes from the patient responded by proliferation to herpes simplex antigen but failed to produce leukocyte migration inhibition factor. Herpes simplex antibody titers increased during active infection. Total hemolytic complement (TCH50), the third (C3), fifth (C5), sixth (C6) and seventh (C7) components of complement, and factor B were dramatically reduced; the first (C1), second (C2) and fourth (C4) components of complement were within normal limits. In family members with a history of recurrent herpes simplex, one or more of the later complement components (C5, C6 or C7) was reduced. This study demonstrates the activation of complement in these serums via the alternative pathway.

Immunocytochemical studies of blood group A, H, I, and i antigens in gastric mucosae of infants with normal gastric histology and of patients with gastric carcinoma and chronic benign peptic ulceration.

Indirect immunofluorescence studies of blood group A, H, I, and i antigens were performed on the gastric mucosae and tumor tissues of patients with gastric carcinoma, on the mucosae of patients with chronic benign gastric ulceration, and on the mucosae of infants who had died of causes other than gastrointestinal disease. The following findings were of particular interest: (1) Normal 'secretor' type mucosae were distinguishable from 'non-secretor' type mucosae by the uniform staining of the A or H antigens at the surface and in the pits. Normal 'non-secretor' type mucosae showed little staining of the H or A antigens but, instead, there was staining with anti-I(Ma) antibody. Staining with anti-I(Step) and anti-i(Den) did not show a clear correlation with the 'secretor'/'non-secretor' status of the normal mucosae. (2) Apparently normal areas of gastric mucosae of patients with gastric carcinoma or the normal part of gastric mucosae of patients with benign gastric ulcer frequently showed focal areas of loss or gain of the blood group antigens as is often seen in gastric carcinoma tissues. (3) In the mucosae of patients with intestinal metaplasia there was marked loss of A/H antigens in 'secretors' and I(Ma) antigen in 'non-secretors'. (4) Staining characteristics of tissues from gastric carcinoma were:(a) Focal loss of the expected A/H or I antigens was observed with much variation in staining from area to area, but only a minority showed complete loss of the expected staining. (b) A majority of the carcinomas from 'secretors' showed foci of substantial staining with anti-I(Ma) in contrast to normal 'secretor' mucosae. This is probably due to incomplete biosynthesis of A/H determinants. (c) Incompatible A-like staining by a rabbit anti-A serum was observed in one out of nine adenocarcinomas from blood group B or O persons. (d) A few cases showed substantial i antigen staining. The aberrant expression of blood group A, H, I, and i antigens in neoplastic as well as in some areas of morphologically normal mucosa of patients with benign and malignant diseases of the stomach is discussed in the context of current biochemical knowledge.

A multi-centre general practitioner assessment of butriptyline hydrochloride ('Evadyne').

A multi-centre open study in general practice was carried out to assess the efficacy of and incidence of side-effects with the tricyclic antidepressant, butriptyline. Of a series of 153 patients with non-psychotic depression, with or without anxiety, 105 (69%) were judged as having a good or fair response to treatment with 75 mg to 150 mg butriptyline daily. Side-effects of an anticholinergic nature were seen in 13.7% of patients, but the incidence decreased to less than 4% in the 101 patients receiving treatment for over 7 weeks.

Long-term follow-up of weight status of subjects in a behavioral weight control program.

Few studies have examined the long-term effectiveness of behavioral weight control programs. Interpretation of the results from these studies has been limited due to small sample size, use of only one sex, and the number of evaluation parameters. A 2-year follow-up study was designed to assess the effectiveness of a behavioral weight control program on 123 obese male and 386 obese female subjects. Body weights were measured by dietitians at baseline and after an 8-week treatment program. Two-year follow-up weights were self-reported from a mailed questionnaire. The subjects' mean weight at baseline was 185.6 +/- 43.4 lb (no. = 509). Their mean percent over ideal body weight at baseline was 29.7%. Following an 8-week treatment period, mean weight was 176.4 +/- 41.3 lb (no. = 509), yielding a mean weight loss of 9.2 +/- 6.4 lb. Weight change after the 8-week treatment period ranged from a loss of 37 lb to a gain of 5 lb. The 2-year follow-up study showed that mean weight of the 498 subjects was 179.8 +/- 42.9 lb, yielding a mean weight loss of 5.8 +/- 15.5 lb. Weight change ranged from a loss of 71 lb to a gain of 47 lb. After 2 years, 325 subjects (65.3%) were still below their baseline weights, 182 subjects (36.6% of the entire study group) had maintained or enhanced the weight loss achieved during treatment, and 80 subjects (16.1%) weighed at least 10% less than their baseline weight.(ABSTRACT TRUNCATED AT 250 WORDS)