5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma

BACKGROUND The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume. METHODS We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis. RESULTS The mean resection cavity (29 cm(3)) was marginally smaller than the pre-operative contrast-enhancing tumor (39 cm(3), p = 0.32). However, the mean overall resection volume (84 cm(3)) was significantly larger than the pre-operative contrast-enhancing tumor (39 cm(3), p = 0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45 cm(3). The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6 mm (range 0-10 mm). CONCLUSIONS Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk.

Volumetric analysis of lung nodules in computed tomography (CT): comparison of two different segmentation algorithm softwares and two different reconstruction filters on automated volume calculation.

BACKGROUND A precise detection of volume change allows for better estimating the biological behavior of the lung nodules. Postprocessing tools with automated detection, segmentation, and volumetric analysis of lung nodules may expedite radiological processes and give additional confidence to the radiologists. PURPOSE To compare two different postprocessing software algorithms (LMS Lung, Median Technologies; LungCARE®, Siemens) in CT volumetric measurement and to analyze the effect of soft (B30) and hard reconstruction filter (B70) on automated volume measurement. MATERIAL AND METHODS Between January 2010 and April 2010, 45 patients with a total of 113 pulmonary nodules were included. The CT exam was performed on a 64-row multidetector CT scanner (Somatom Sensation, Siemens, Erlangen, Germany) with the following parameters: collimation, 24x1.2 mm; pitch, 1.15; voltage, 120 kVp; reference tube current-time, 100 mAs. Automated volumetric measurement of each lung nodule was performed with the two different postprocessing algorithms based on two reconstruction filters (B30 and B70). The average relative volume measurement difference (VME%) and the limits of agreement between two methods were used for comparison. RESULTS At soft reconstruction filters the LMS system produced mean nodule volumes that were 34.1% (P < 0.0001) larger than those by LungCARE® system. The VME% was 42.2% with a limit of agreement between -53.9% and 138.4%.The volume measurement with soft filters (B30) was significantly larger than with hard filters (B70); 11.2% for LMS and 1.6% for LungCARE®, respectively (both with P < 0.05). LMS measured greater volumes with both filters, 13.6% for soft and 3.8% for hard filters, respectively (P < 0.01 and P > 0.05). CONCLUSION There is a substantial inter-software (LMS/LungCARE®) as well as intra-software variability (B30/B70) in lung nodule volume measurement; therefore, it is mandatory to use the same equipment with the same reconstruction filter for the follow-up of lung nodule volume.

Macrocerebellum: Significance and Pathogenic Considerations

Macrocerebellum is a rare finding characterized by an abnormally large cerebellum. Only few patients with a syndromal or isolated macrocerebellum have been reported so far. This article aims to categorize the magnetic resonance imaging (MRI) findings, quantitate the macrocerebellum by volumetric analysis, characterize the neurological and dysmorphic features and cognitive outcome, and report the results of genetic analyses in children with macrocerebellum. All MR images were qualitatively evaluated for infratentorial and supratentorial abnormalities. Volumetric analysis was performed. Data about neurological and dysmorphic features, outcome, and genetic analysis were collected from clinical histories and follow-up examinations. Five patients were included. Volumetric analysis in three patients confirmed large cerebellar size compared to age-matched controls. MR evaluation showed that thickening of the cortical gray matter of the cerebellar hemispheres is responsible for the macrocerebellum. Additional infratentorial and supratentorial abnormalities were present in all patients. Muscular hypotonia, as well as impaired motor and cognitive development, was found in all patients, with ocular movement disorders in three of five patients. The five patients differed significantly in terms of dysmorphic features and involvement of extracerebral organs. Submicroscopic chromosomal aberrations were found in two patients. Macrocerebellum is caused by thickening of the cortical gray matter of the cerebellar hemispheres, suggesting that cerebellar granule cells may be involved in its development. Patients with macrocerebellum show highly heterogeneous neuroimaging, clinical, and genetic findings, suggesting that macrocerebellum is not a nosological entity, but instead represents the structural manifestation of a deeper, more basic biological disturbance common to heterogeneous disorders.

Quantitative analysis of O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

Methylation of the MGMT promoter is supposed to be a predictive and prognostic factor in glioblastoma. Whether MGMT promoter methylation correlates with tumor response to temozolomide in low-grade gliomas is less clear. Therefore, we analyzed MGMT promoter methylation by a quantitative methylation-specific PCR in 22 patients with histologically verified low-grade gliomas (WHO grade II) who were treated with temozolomide (TMZ) for tumor progression. Objective tumor response, toxicity, and LOH of microsatellite markers on chromosomes 1p and 19q were analyzed. Histological classification revealed ten oligodendrogliomas, seven oligoastrocytomas, and five astrocytomas. All patients were treated with TMZ 200 mg/m2 on days 1-5 in a 4 week cycle. The median progression-free survival was 32 months. Combined LOH 1p and 19q was found in 14 patients; one patient had LOH 1p alone and one patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. LOH 1p and/or 19q correlated with longer time to progression but not with radiological response to TMZ. MGMT promoter methylation was detectable in 20 patients by conventional PCR and quantitative analysis revealed the methylation status was between 12 and 100%. The volumetric response to chemotherapy analyzed by MRI and time to progression correlated with the level of MGMT promoter methylation. Therefore, our retrospective case series suggests that quantitative methylation-specific PCR of the MGMT promoter predicts radiological response to chemotherapy with TMZ in WHO grade II gliomas.

Analysis of 3D Soft Tissue Changes After 1- and 2-Jaw Orthognathic Surgery in Mandibular Prognathism Patients

Purpose Orthognathic surgery has the objective of altering facial balance to achieve esthetic results in patients who have severe disharmony of the jaws. The purpose was to quantify the soft tissue changes after orthognathic surgery, as well as to assess the differences in 3D soft tissue changes in the middle and lower third of the face between the 1- and 2-jaw surgery groups, in mandibular prognathism patients. Materials and Methods We assessed soft tissue changes of patients who have been diagnosed with mandibular prognathism and received either isolated mandibular surgery or bimaxillary surgery. The quantitative surface displacement was assessed by superimposing preoperative and postoperative volumetric images. An observer measured a surface-distance value that is shown as a contour line. Differences between the groups were determined by the Mann-Whitney U test. The Spearman correlation coefficient was used to evaluate a potential correlation between patients' surgical and cephalometric variables and soft tissue changes after orthognathic surgery in each group. Results There were significant differences in the middle third of the face between the 1- and 2-jaw surgery groups. Soft tissues in the lower third of the face changed in both surgery groups, but not significantly. The correlation patterns were more evident in the lower third of the face. Conclusion The overall soft tissue changes of the midfacial area were more evident in the 2-jaw surgery group. In 2-jaw surgery, significant changes would be expected in the midfacial area, but caution should be exercised in patients who have a wide alar base.

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R2 improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.

Pulmonary lymphangioleiomyomatosis: analysis of disease manifestation by region-based quantification of lung parenchyma

PURPOSE Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). MATERIALS AND METHODS CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a "peel" and "core" of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density <-950HU to the total number of voxels in the lung. RESULTS Cystic changes accounted for 0.1-39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p=0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower third: median 13.4, upper and middle thirds: median 19.0, p=0.001). CONCLUSION The distribution of cystic lesions in LAM is significantly more pronounced in the central lung compared to peripheral areas. There is a significant predominance of cystic changes in apical and intermediate lung zones compared to the lung bases.

Analysis of analogue models by helical X-ray computed tomography

The aim of analogue model experiments in geology is to simulate structures in nature under specific imposed boundary conditions using materials whose rheological properties are similar to those of rocks in nature. In the late 1980s, X-ray computed tomography (CT) was first applied to the analysis of such models. In early studies only a limited number of cross-sectional slices could be recorded because of the time involved in CT data acquisition, the long cooling periods for the X-ray source and computational capacity. Technological improvements presently allow an almost unlimited number of closely spaced serial cross-sections to be acquired and calculated. Computer visualization software allows a full 3D analysis of every recorded stage. Such analyses are especially valuable when trying to understand complex geological structures, commonly with lateral changes in 3D geometry. Periodic acquisition of volumetric data sets in the course of the experiment makes it possible to carry out a 4D analysis of the model, i.e. 3D analysis through time. Examples are shown of 4D analysis of analogue models that tested the influence of lateral rheological changes on the structures obtained in contractional and extensional settings.

Multimodal Imaging and Choroidal Volumetric Changes After Half-fluence PDT in Central Serous Chorioretinopathy.

PURPOSE The purpose of this study was to identify SD-OCT changes that correspond to leakage on fluorescein (FA) and indocyanine angiography (ICGA) and evaluate effect of half-fluence photodynamic therapy (PDT) on choroidal volume in chronic central serous choroidoretinopathy (CSC). METHODS Retrospective analysis of patients with chronic CSC who had undergone PDT. Baseline FA and ICGA images were overlaid on SD-OCT to identify OCT correlates of FA or ICGA hyperfluorescence. Choroidal volume was evaluated in a subgroup of eyes before and after PDT. RESULTS Twenty eyes were evaluated at baseline, of which seven eyes had choroidal volume evaluations at baseline and 3 months following PDT. SD-OCT changes corresponding to FA hyperfluorescence were subretinal fluid (73%), RPE microrip (50%), RPE double-layer sign (31%), RPE detachment (15%), and RPE thickening (8%). ICGA hyperfluoresence was correlated in 93% with hyperreflective spots in the superficial choroid. Choroidal volume decreased from 9.35 ± 1.99 to 8.52 ± 1.92 and 8.04 ± 1.7 mm(3) (at 1 and 3 months post PDT, respectively, p ≤ 0.001). CONCLUSIONS We identified specific OCT findings that correlate with FA and ICGA leakage sites. SD-OCT is a valuable tool to localize CSC lesions and may be useful to guide PDT treatment. Generalized choroidal volume decrease occurs following PDT and extends beyond PDT treatment site.