Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

Rapid survey protocol that provides dynamic information on reef condition to managers of the Great Barrier Reef.

Managing to support coral reef resilience as the climate changes requires strategic and responsive actions that reduce anthropogenic stress. Managers can only target and tailor these actions if they regularly receive information on system condition and impact severity. In large coral reef areas like the Great Barrier Reef Marine Park (GBRMP), acquiring condition and impact data with good spatial and temporal coverage requires using a large network of observers. Here, we describe the result of ~10 years of evolving and refining participatory monitoring programs used in the GBR that have rangers, tourism operators and members of the public as observers. Participants complete Reef Health and Impact Surveys (RHIS) using a protocol that meets coral reef managers' needs for up-to-date information on the following: benthic community composition, reef condition and impacts including coral diseases, damage, predation and the presence of rubbish. Training programs ensure that the information gathered is sufficiently precise to inform management decisions. Participants regularly report because the demands of the survey methodology have been matched to their time availability. Undertaking the RHIS protocol we describe involves three ~20 min surveys at each site. Participants enter data into an online data management system that can create reports for managers and participants within minutes of data being submitted. Since 2009, 211 participants have completed a total of more than 10,415 surveys at more than 625 different reefs. The two-way exchange of information between managers and participants increases the capacity to manage reefs adaptively, meets education and outreach objectives and can increase stewardship. The general approach used and the survey methodology are both sufficiently adaptable to be used in all reef regions.

Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison.

BACKGROUND AND PURPOSE: Studies consistently report lower ADC values in isocitrate dehydrogenase (IDH) wild-type gliomas than in IDH mutant tumors, but their methods and thresholds vary. This research aimed to compare volumetric and regional ADC measurement techniques for glioma genotyping, with a focus on IDH status prediction. MATERIALS AND METHODS: Treatment-naïve World Health Organization grade II and III gliomas were analyzed by 3 neuroradiologist readers blinded to tissue results. ADC minimum and mean ROIs were defined in tumor and in normal-appearing white matter to calculate normalized values. T2-weighted tumor VOIs were registered to ADC maps with histogram parameters (mean, 2nd and 5th percentiles) extracted. Nonparametric testing (eta2 and ANOVA) was performed to identify associations between ADC metrics and glioma genotypes. Logistic regression was used to probe the ability of VOI and ROI metrics to predict IDH status. RESULTS: The study included 283 patients with 79 IDH wild-type and 204 IDH mutant gliomas. Across the study population, IDH status was most accurately predicted by ROI mean normalized ADC and VOI mean normalized ADC, with areas under the curve of 0.83 and 0.82, respectively. The results for ROI-based genotyping of nonenhancing and solid-patchy enhancing gliomas were comparable with volumetric parameters (area under the curve = 0.81-0.84). In rim-enhancing, centrally necrotic tumors (n = 23), only volumetric measurements were predictive (0.90). CONCLUSIONS: Regional normalized mean ADC measurements are noninferior to volumetric segmentation for defining solid glioma IDH status. Partially necrotic, rim-enhancing tumors are unsuitable for ROI assessment and may benefit from volumetric ADC quantification.

A strategic framework for responding to coral bleaching events in a changing climate.

The frequency and severity of mass coral bleaching events are predicted to increase as sea temperatures continue to warm under a global regime of rising ocean temperatures. Bleaching events can be disastrous for coral reef ecosystems and, given the number of other stressors to reefs that result from human activities, there is widespread concern about their future. This article provides a strategic framework from the Great Barrier Reef to prepare for and respond to mass bleaching events. The framework presented has two main inter-related components: an early warning system and assessment and monitoring. Both include the need to proactively and consistently communicate information on environmental conditions and the level of bleaching severity to senior decision-makers, stakeholders, and the public. Managers, being the most timely and credible source of information on bleaching events, can facilitate the implementation of strategies that can give reefs the best chance to recover from bleaching and to withstand future disturbances. The proposed framework is readily transferable to other coral reef regions, and can easily be adapted by managers to local financial, technical, and human resources.

Effects of microgravity on the composition of the intervertebral disk.

The lumbar annuli of rats flown on COSMOS 2044 were compared with those of three control groups and a tail-suspension experimental model. The wet and dry weights of the annuli were significantly smaller (P less than 0.05) in the flight group than in three control groups. The collagen-to-proteoglycan ratio was significantly greater (P less than 0.001) in the flight group than in the three control groups, but there were no detectable changes in the relative proportions of type I and II collagen or in the number of pyridinoline cross-links. When the annuli were immersed in water for 2 h, more proteoglycans (P less than 0.001) leached from the annuli of flown rats than from the tissue of control animals, suggesting abnormal or smaller proteoglycans. Safranin-O indicated a normal spatial distribution of the proteoglycans within the annulus. Tail suspension did not affect the size of the annuli, but more proteoglycans (P less than 0.05) leached from the tissue of suspended animals than from the normal annuli. The reasons for smaller disks and the abnormal ratio between the fibrous collagenous network and the proteoglycan gel in the flight group are unknown at this time. It is, however, probable that these changes may affect the biomechanical functions of the annulus, although they may be temporary and totally reversible if injuries are avoided in the interim period.

Structural and mechanical adaptation of immature bone to strenuous exercise.

To investigate the adaptive responses of immature bone to increased loads, young (3-wk-old) White Leghorn roosters were subjected to moderately intense treadmill running for 5 or 9 wk. The training program induced significant increases in maximal O2 consumption and muscle fumarase activity in the 12-wk-old birds, demonstrating that growing chickens have the ability to enhance their aerobic capacity. The structural and mechanical properties of the runners' tarsometatarsus bones were compared with sedentary age-matched controls at 8 and 12 wk of age. Suppression of circumferential growth occurred with exercise at both ages, whereas exercise enhanced middiaphysial cortical thickening, especially on the bones' concave surfaces. Although cross-sectional area moments of inertia did not change with exercise, significant decreases in bending stiffness, energy to yield, and energy to fracture were observed. It was concluded that strenuous exercise may retard long-bone maturation, resulting in more compliant bones.

Response of immature chicken meniscus to strenuous exercise: biochemical studies of proteoglycan and collagen.

Male white Leghorn chickens were exercised on a treadmill at 70-80% of their maximal oxygen consumption starting at 4 weeks and continuing up to 20 weeks of age. The effect of the strenuous exercise regime on the extracellular matrix of menisci was followed through studies of proteoglycans and collagen. Avian menisci contain type I collagen, chondroitin sulfate proteoglycans, which increase with age in amount and degree of aggregation, and dermatan sulfate proteoglycans, which decrease with age. Five weeks of exercise cause a premature decrease of dermatan sulfate proteoglycans, while the chondroitin sulfate-containing molecules become significantly more aggregated than those of the tissue of age-matched controls. Strenuous exercise also causes a significant decrease in the number of pyridinoline crosslinks per mole of collagen in the menisci of young runners. The exercise-induced changes of proteoglycan and collagen occur only during the period of active growth, and all parameters return to normal when the animals reach skeletal maturity. The early proteoglycan aggregation and dermatan sulfate decrease induced by exercise are probably an adaptation to the increased loading. Although the mechanism by which strenuous exercise reduces or delays the formation of collagen pyridinoline crosslinks in menisci of skeletally immature animals is unknown, their decrease could negatively affect the mechanical properties of the tissue during the period of active growth.

Morphological and biochemical effects of sodium morrhuate on tendons.

The purpose of this study was to determine some of the morphological and biochemical effects of sodium morrhuate injections into intact rabbit patellar tendons and Achilles tendons. The effects of one, three, and five 100 microliters injections of sodium morrhuate on tendon circumference, cell content, collagen fibril diameter, collagen-proteoglycan relationships, water content, amino sugar content, and hydroxyproline content were investigated over periods of 1, 4, and 9 weeks. In general, sodium morrhuate injected tendons were larger in diameter and contained more cells, smaller collagen fibrils, increased water and amino sugar content, and reduced hydroxyproline content compared with their contralateral controls. As a sclerosing agent, sodium morrhuate appears to mimic the early stages of an injury-repair sequence when injected directly into intact tendons. Whether sodium morrhuate may hasten repair responses or improve joint laxity remains to be determined.

Spatial and temporal expression of CD44 isoforms in the developing and growing joints of the rat limb.

Hyaluronan is an integral component of proteoglycan-rich extracellular matrices such as hyaline cartilage. Hyaluronan is commonly found in embryonic tissue and is important in the formation of hydrated matrices that allow cellular expansion and migration. Cell surface hyaluronan-binding proteins such as CD44 are presumed to be important in the cellular interactions with hyaluronan in both of these processes. The primary aim of this study was to document the spatial and temporal expressions of CD44 isoforms during the development and growth of the diarthrodial joints of rat limbs. With use of in situ hybridization and immunohistochemistry, the CD44s isoform is selectively identified as localized to a single cell layer on opposing sides of the joint at the first appearance of joint cavitation (on the 18th day of gestation). After joint formation in the neonate, the expression of the CD44s isoform in the cells at the joint surface is lost. These findings suggest that the CD44s isoform has a role in the development of the diarthrodial joint, presumably through interaction with hyaluronan.

Pseudoachondroplasia: biochemical and histochemical studies of cartilage.

Cartilage from patients with pseudoachondroplasia is characterized by unique inclusions in the cisternae of the endoplasmic reticulum and proteoglycan abnormalities have been suggested in this form of dwarfism. To elucidate the nature of the proteoglycan defect, we determined the amount of the individual glycosaminoglycans present in iliac-crest cartilage of three patients and extracted the proteoglycan monomers from one of the samples. Sections of iliac-crest cartilage and proximal fibular growth plates were examined by electron microscopy and also stained with hematoxylin and eosin, safranin O-fast green, and alcian blue in the presence of increasing concentrations of magnesium chloride (zero to one molar). The chondrocytes of the iliac crest and fibular physes were arranged in clusters more than in columns and contained characteristic endoplasmic reticulum inclusions, which were particularly large in the hypertrophic cells. The cartilage stained very poorly with hematoxylin and eosin and with safranin O-fast green. The alcian-blue stain was abolished from perilacunar areas and from longitudinal septa by magnesium chloride concentrations that were lower than those required by normal tissue. The proteoglycans of iliac-crest cartilage were found to be significantly enriched in keratan sulphate and had a below-normal ratio of chondroitin-4-sulphate to chondroitin-6-sulphate, although the amount of the two isomeric chondroitin sulphates combined was within normal limits. The urinary excretion of glycosaminoglycan by the three patients was normal. Pseudoachondroplasia appears to be a generalized cartilage disorder involving abnormalities of proteoglycans, probably related to the core protein or to enzymes that are responsible for the formation of the glycosaminoglycan chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Elastic fibers in human intervertebral discs.

Although previous studies failed to demonstrate elastic fibers in intervertebral discs, electron microscopy of twenty human intervertebral discs obtained at autopsy and operation revealed characteristic elastic fibers in both the annulus fibrosus and the nucleus pulposus. Their contribution to the mechanical properties of the intervertebral disc remains to be determined.

Legg-Calvé-Perthes disease. Histochemical and ultrastructural observations of the epiphyseal cartilage and physis.

UNLABELLED: Biopsy specimens of the lateral aspect of the femoral head and neck were obtained from five children with Legg-Calvé-Perthes disease and were studied using histochemistry and electron microscopy. Beneath the normal articular cartilage there was a thick zone of hyaline (epiphyseal) cartilage containing sharply demarcated areas of hypercellular and fibrillated cartilage with prominent blood vessels. The fibrillated cartilage was strongly positive to alcian blue, weakly positive to periodic acid-Schiff, and positive to aniline blue. The interterritorial matrix in the hypercellular areas was weakly positive to both alcian blue and periodic acid-Schiff. Ultrastructural examination of these areas revealed many irregularly oriented large collagen fibrils and variable amounts of proteoglycan granules. These results suggest that in the fibrillar areas there are: (1) a high proteoglycan content, (2) a decrease in structural glycoproteins, and (3) a different size of collagen fibrils from that of normal epiphyseal cartilage. The hypercellular areas had a decrease in proteoglycans, glycoproteins, and collagen. The lateral physeal margin was often irregular, with a marked reduction of collagen and proteoglycan granules, and contained numerous large lipid inclusions. CLINICAL RELEVANCE: The abnormal areas in the epiphyseal cartilage of patients with Legg-Calvé-Perthes disease have different histochemical and structural properties from normal cartilage and from fibrocartilage. This suggests that the disease could be a localized expression of a generalized, transient disorder of epiphyseal cartilage that is responsible for delayed skeletal maturation. The cartilage lesions are similar to those seen in the vertebral plates in patients with juvenile kyphosis. Whether the epiphyseal cartilage abnormalities are primary or are secondary to ischemia remains uncertain; however, it appears that the collapse and necrosis of the femoral head could result from the breakdown and disorganization of the matrix of the epiphyseal cartilage, followed by abnormal ossification.

The ultrastructure of the growth plate in slipped capital femoral epiphysis.

Core biopsy specimens of the proximal femoral growth plate from three patients with slipped capital femoral epiphysis were studied by light and electron microscopy. In the resting zone, the cartilage matrix was composed of large, densely packed collagen fibrils. The cartilage matrix in the zones of chondrocyte hypertrophy where the slippage occurred contained only scattered fine collagen fibrils in a homogeneous ground substance. The change in composition of cartilage matrix in the distal region of the epiphyseal plate may predispose that region to slippage.

Survival of implanted irradiated cartilage.

As a result of our study the following conclusions may be drawn: 1. Irradiated homograft costal cartilage appears to survive as a nonviable implant in part replaced by host tissue in the cat. 2. Such replacement may be minimized by leaving as much perichondrium intact as is feasible. 3. Boiling or freezing fresh autogenous cartilage in an attempt to alter its warping characteristics is asking for increased resorption.

Localization of acid and alkaline phosphatase activities in the blood vessels of normotensive and hypertensive rats.

Samples of aortae and caudal arteries from normotensive and hypertensive rats were studied for cytochemical and biochemical determinations of acid and alkaline phosphatase activities. Cytochemical examination revealed an increased amount of acid phosphatase reaction product in hypertensive samples, with extensive localization to the extracellular matrix. Alkaline phosphatase activity was localized to the plasma membrane of fibroblasts and vascular smooth muscle cells and to the extracellular matrix. Biochemical assays of enzyme activities supported the cytochemical findings, showing increased activity in aortae from hypertensive rats.

Effects of 2 weeks hypergravity on the composition of the intervertebral disc.

BACKGROUND: The effects of loading on connective tissues similar to the intervertebral disk have primarily been studied using articular cartilage organ culture in vitro techniques. The effects of in vivo loading on the intervertebral disk are less well documented. METHODS: The lumbar annuli of rats centrifuged at 2G for 2 wk were compared with those of similar rats kept under analogous conditions at 1G. The studies involved the water, hydroxyproline (collagen), and uronic acid (proteoglycan, PG) content of the L4-5 and L5-6 annuli. Comparisons were also made between the 2G animals and the previous Cosmos 2044 spaceflight animals at 0G. RESULTS: The water content of annuli did not differ between the control and 2G annuli; however, the PG content of the tissue was decreased in the 2G animals and the collagen content slightly increased, resulting in an increased collagen-PG ratio in the 2G animals. When the annuli were immersed in water for 2 h, more PG leached from the annuli of the 2G animals than the control animals, suggesting an alteration in the nature of the PG population comprising the annuli. Interestingly, the direction of changes in the 2G annuli was identical to that of the previous Cosmos 2044 0G animals when they were compared with their respective controls. Therefore, directly opposite experimental conditions (2G and 0G) produced similar results. CONCLUSION: Previous studies regarding PG synthesis and content in cartilaginous tissues suggest alterations in intratissue pH and hydration to be among the factors involved in controlling the PG population. If the observed changes are permanent, they may affect the integrity of the intervertebral disk although it is likely they are totally reversible on return to 1G after an interim period, providing injuries are avoided.

Suture extrusion in small arteries and veins.

One longitudinally orientated microsuture was implanted in the femoral artery and vein of 40 rats and harvested at 4 different time intervals (2, 8, 12, 18 weeks). The tissue section containing the most luminal portion of suture loop was chosen and submitted for analysis. Two parameters, one estimating the suture location in the vessel wall relative to the internal elastic lamina (IEL) and a second, estimating the magnitude of the intimal response at the suture site were addressed. Average suture location changed significantly over time. The suture tended to be exteriorized or extruded from its once luminal location within the intima to a position located within the adventitia. Veins exhibited a greater incidence of suture extrusion than arteries. The maximum magnitude of the intimal cellular response occurred in the 2 week time interval. Significant decreases (p less than 0.05) in the thickness of the intima was observed in each subsequent time interval for both arteries and veins. The results of this experiment indicate that the cellular response and reparative processes occurring in small arteries and veins modifies the luminal papillary projection and extrudes nylon suture material.

The effects of space flight on the composition of the intervertebral disc.

The lumbar annuli of rats flown on a COSMOS space flight were compared with those of three control groups and a ground antigravity tail suspension model. The wet and dry weights of the space flight annuli were significantly smaller than the three control groups. In addition, the collagen-to-proteoglycan ratio was significantly greater in the flight group due to a proportional increase in collagen and a decrease in proteoglycan. Finally, it appears microgravity may have altered the nature of the proteoglycan population as more proteoglycans leached from the annuli of flight animals than control animals when immersed in water.

Morphological and biochemical effects of strenuous exercise on immature long bones.

To determine the effects of intense exercise on the growth of long bones in immature animals, young male white leghorn chickens were run five days per week starting at four weeks of age on motor-driven treadmills. Work intensity was determined on the basis of maximal oxygen consumption (VO2 max) with the exercise intensity maintained at 70-80 percent VO2 max. Young animals ran continuously for 30 minutes, older animals 45 to 60 minutes each day. Runners and controls (10 animals per group) were sacrificed at 8, 12, 14 and 20 weeks of age. The lengths of the femurs and tibiotarsus were significantly stunted at 8-, 12- and 14 weeks in the runners but had nearly recovered at 20 weeks of age. Both bones also demonstrated significantly decreased total cross-sectional areas in 8-, 12- and 14 week-old runners as well as decreased cortical cross-sectional areas. The tibiotarsus also remained significantly smaller in the 20-week-old runners, but the femur had recovered in terms of radial growth. Intermolecular pyridinoline collagen crosslinks were identical in amount in the two groups with the femur collagen significantly less cross-linked than the tibiotarsus. The delayed growth of the exercised avian young bone is consistent with data obtained from children and young mammalian models. The osteogenic response to exercise that produces an increased bone mass in adult tissue appears either suppressed or overcome in young avian bone indicating that it may be erroneous to assume that data obtained from adult tissue are also applicable to young growing bone.