Michal Schneider-Kolsky

White matter fiber tractography: why we need to move beyond DTI.

OBJECT Diffusion-based MRI tractography is an imaging tool increasingly used in neurosurgical procedures to generate 3D maps of white matter pathways as an aid to identifying safe margins of resection. The majority of white matter fiber tractography software packages currently available to clinicians rely on a fundamentally flawed framework to generate fiber orientations from diffusion-weighted data, namely diffusion tensor imaging (DTI). This work provides the first extensive and systematic exploration of the practical limitations of DTI-based tractography and investigates whether the higher-order tractography model constrained spherical deconvolution provides a reasonable solution to these problems within a clinically feasible timeframe. METHODS Comparison of tractography methodologies in visualizing the corticospinal tracts was made using the diffusion-weighted data sets from 45 healthy controls and 10 patients undergoing presurgical imaging assessment. Tensor-based and constrained spherical deconvolution-based tractography methodologies were applied to both patients and controls. RESULTS Diffusion tensor imaging-based tractography methods (using both deterministic and probabilistic tractography algorithms) substantially underestimated the extent of tracks connecting to the sensorimotor cortex in all participants in the control group. In contrast, the constrained spherical deconvolution tractography method consistently produced the biologically expected fan-shaped configuration of tracks. In the clinical cases, in which tractography was performed to visualize the corticospinal pathways in patients with concomitant risk of neurological deficit following neurosurgical resection, the constrained spherical deconvolution-based and tensor-based tractography methodologies indicated very different apparent safe margins of resection; the constrained spherical deconvolution-based method identified corticospinal tracts extending to the entire sensorimotor cortex, while the tensor-based method only identified a narrow subset of tracts extending medially to the vertex. CONCLUSIONS This comprehensive study shows that the most widely used clinical tractography method (diffusion tensor imaging-based tractography) results in systematically unreliable and clinically misleading information. The higher-order tractography model, using the same diffusion-weighted data, clearly demonstrates fiber tracts more accurately, providing improved estimates of safety margins that may be useful in neurosurgical procedures. We therefore need to move beyond the diffusion tensor framework if we are to begin to provide neurosurgeons with biologically reliable tractography information.

Magnetic Resonance Imaging Parameters for Assessing Risk of Recurrent Hamstring Injuries in Elite Athletes

Background Magnetic resonance (MR) imaging has established its usefulness in diagnosing hamstring muscle strain and identifying features correlating with the duration of rehabilitation in athletes; however, data are currently lacking that may predict which imaging parameters may be predictive of a repeat strain. Purpose This study was conducted to identify whether any MR imaging-identifiable parameters are predictive of athletes at risk of sustaining a recurrent hamstring strain in the same playing season. Study Design Cohort study; Level of evidence, 3. Methods Forty-one players of the Australian Football League who sustained a hamstring injury underwent MR examination within 3 days of injury between February and August 2002. The imaging parameters measured were the length of injury, cross-sectional area, the specific muscle involved, and the location of the injury within the muscle-tendon unit. Players who suffered a repeat injury during the same season were reimaged, and baseline and repeat injury measurements were compared. Comparison was also made between this group and those who sustained a single strain. Results Forty-one players sustained hamstring strains that were positive on MR imaging, with 31 injured once and 10 suffering a second injury. The mean length of hamstring muscle injury for the isolated group was 83.4 mm, compared with 98.7 mm for the reinjury group (P = .35). In the reinjury group, the second strain was also of greater length than the original (mean, 107.5 mm; P = .07). Ninety percent of players sustaining a repeat injury demonstrated an injury length greater than 60 mm, compared with only 58% in the single strain group (P = .01). Only 7% of players (1 of 14) with a strain <60 mm suffered a repeat injury. Of the 27 players sustaining a hamstring strain >60 mm, 33% (9 of 27) suffered a repeat injury. Of all the parameters assessed, only a history of anterior cruciate ligament sprain was a statistically significant predictor for suffering a second strain during the same season of competition. Conclusion A history of anterior cruciate ligament injury was the only statistically significant risk factor for a recurrent hamstring strain in our study. Of the imaging parameters, the MR length of a strain had the strongest correlation association with a repeat hamstring strain and therefore may assist in identifying which athletes are more likely to suffer further reinjury.

A Comparison Between Clinical Assessment and Magnetic Resonance Imaging of Acute Hamstring Injuries

Background Physicians evaluating hamstring strains in professional football players are increasingly turning to magnetic resonance imaging to support the clinical diagnosis and management of the injury. However, little information is available to assess how magnetic resonance imaging compares with the clinical evaluation in establishing the duration of rehabilitation required. Hypothesis Magnetic resonance imaging of hamstring strains can be useful in determining duration of rehabilitation. Study Design Cohort study (Diagnosis); Level of evidence, 1. Methods Fifty-eight professional football players with a diagnosis of hamstring injury made by the team physician were enrolled in the study. All players underwent magnetic resonance imaging and a clinical evaluation by an independent physical therapist within 3 days of the injury. Presence, type, and location of injury were recorded in each examination. The physical therapist estimated the time required until return to competition, and the radiologist used the length of the injury (coronal view) to establish rehabilitation duration. Both clinicians were blinded to the other modality. Results Clinical and magnetic resonance imaging assessments were in agreement in 38 of 58 cases (65.5%). In 18 cases (31.0%), a clinically positive diagnosis was made, but no abnormalities were evident on magnetic resonance imaging. In 2 cases (3.4%), magnetic resonance imaging detected an injury, whereas the clinical examination had negative or equivocal findings. Both clinical examination and magnetic resonance imaging findings were strongly correlated with the actual time required to return to competition (r = .69, P < .001 and r = .58, P < .001, respectively). The correlation coefficient between clinical predictions and magnetic resonance imaging findings was moderate (r = .36, P = .006). Conclusion This study shows that magnetic resonance imaging is not required for estimating the duration of rehabilitation of an acute minor or moderate hamstring injury in professional football players.

Clinical predictors of time to return to competition and of recurrence following hamstring strain in elite Australian footballers

Objective To investigate early clinical predictors of time to return to competition and of recurrence following hamstring strain. Design Prospective observational study. Setting Elite level of Australian football competition. Participant 59 players who suffered a hamstring strain in 2002 season. Predictors Clinical assessment by a physiotherapist and questionnaire. Main outcome measures Time taken to return to play and recurrence of hamstring injury within 3 weeks. Results Players taking more than 1 day to walk pain-free were significantly more likely (p=0.018) to take longer than 3 weeks to return to competition (adjusted odds ratio 4.0; 95% CI 1.3 to 12.6). Nine players (15.2%) experienced an injury recurrence, all involving the biceps femoris. Recurrence was more likely in players who reported a hamstring injury in the past 12 months (adjusted odds ratio 19.6; 95% CI 1.5 to 261.0; p=0.025). Conclusion Time to walk pain-free and previous hamstring injury are predictors of time to return to competition and recurrence, respectively, and should be included in a clinical assessment to aid in prognosis.

High rates of tumor growth and disease progression detected on serial pretreatment fluorodeoxyglucose-positron emission tomography/computed tomography scans in radical radiotherapy candidates with nonsmall cell lung cancer.

The authors studied growth and progression of untreated nonsmall cell lung cancer (NSCLC) by comparing diagnostic and radiotherapy (RT) planning fluorodeoxyglucose (FDG)‐positron emission tomography (PET)/computed tomography (CT) scans before proposed radical chemo‐RT.

Maternal serum total activin A and follistatin in pregnancy and parturition

Objective To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour

The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer

Background Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). Methods A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. Results We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). Conclusions Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

Validation of a 4D-PET maximum intensity projection for delineation of an internal target volume

PURPOSE The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. METHODS AND MATERIALS A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of (18)F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom while moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. RESULTS The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. CONCLUSION A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently underestimates ITV when compared with 4D PET/CT for a lesion affected by respiration.

Maternal serum activin A levels in association with intrauterine fetal growth restriction

Objective To assess maternal serum activin A as a potential marker of fetal growth restriction.

Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy.

Background Renal insufficiency is associated with the development of cardiovascular disease. Objectives This study investigated whether reduced fetal renal mass resulted in renal insufficiency, hypertension, cardiac dysfunction and whether these changes progressed with age. Methods and results Fetal uninephrectomy was performed at 100-day gestation (term, 150 days) and studies performed in male sheep from 6 weeks to 24 months of age. Renal function declined with age in sham animals as demonstrated by increasing plasma creatinine levels and urinary excretion of albumin. The age-related decline in renal function was exacerbated in animals that had undergone fetal uninephrectomy. Evidence of renal insufficiency was indicated from as early as 6 weeks of age with elevations in plasma creatinine (Ptreatment < 0.001), urea (Ptreatment < 0.001) and sodium (Ptreatment < 0.05) levels in uninephrectomized lambs as compared with sham animals. At 6 months, urinary albumin excretion (P < 0.001) was increased and urinary sodium excretion (P < 0.001) decreased in the uninephrectomized animals. By 24 months, renal function had deteriorated further with significant progression of albuminuria (Ptreatment×age < 0.001). Elevation of mean arterial pressure (∼15 mmHg) was associated with significantly increased cardiac output, stroke volume and plasma volume at 6 months; arterial pressure (∼27 mmHg) had increased further in uninephrectomized animals at 24 months and was driven by increased total peripheral resistance. Cardiac functional reserve (dobutamine challenge) was reduced in uninephrectomized animals at 6 and 24 months of age (Ptreatment < 0.001), and this was associated with left ventricular enlargement (P < 0.001) and reduced fractional shortening (P < 0.01). Conclusion Fetal uninephrectomy causing a reduction in nephron endowment results in an accelerated age-related decline in renal function. This is associated with an early onset of elevated blood pressure and impairments in cardiac structure and function.