Self-supervised learning for automated anatomical tracking in medical image data with minimal human labeling effort.

BACKGROUND AND OBJECTIVE: Tracking of anatomical structures in time-resolved medical image data plays an important role for various tasks such as volume change estimation or treatment planning. State-of-the-art deep learning techniques for automated tracking, while providing accurate results, require large amounts of human-labeled training data making their wide-spread use time- and resource-intensive. Our contribution in this work is the implementation and adaption of a self-supervised learning (SSL) framework that addresses this bottleneck of training data generation. METHODS: To this end we adapted and implemented an SSL framework that allows for automated anatomical tracking without the necessity for human-labeled training data. We evaluated this method by comparison to conventional- and deep learning optical flow (OF)-based tracking methods. We applied all methods on three different time-resolved medical image datasets (abdominal MRI, cardiac MRI, and echocardiography) and assessed their accuracy regarding tracking of pre-defined anatomical structures within and across individuals. RESULTS: We found that SSL-based tracking as well as OF-based methods provide accurate results for simple, rigid and smooth motion patterns. However, regarding more complex motion, e.g. non-rigid or discontinuous motion patterns in the cardiac region, and for cross-subject anatomical matching, SSL-based tracking showed markedly superior performance. CONCLUSION: We conclude that automated tracking of anatomical structures on time-resolved medical image data with minimal human labeling effort is feasible using SSL and can provide superior results compared to conventional and deep learning OF-based methods.

Weakly supervised segmentation of tumor lesions in PET-CT hybrid imaging.

Purpose: We introduce and evaluate deep learning methods for weakly supervised segmentation of tumor lesions in whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) based solely on binary global labels ("tumor" versus "no tumor"). Approach: We propose a three-step approach based on (i) a deep learning framework for image classification, (ii) subsequent generation of class activation maps (CAMs) using different CAM methods (CAM, GradCAM, GradCAM++, ScoreCAM), and (iii) final tumor segmentation based on the aforementioned CAMs. A VGG-based classification neural network was trained to distinguish between PET image slices with and without FDG-avid tumor lesions. Subsequently, the CAMs of this network were used to identify the tumor regions within images. This proposed framework was applied to FDG-PET/CT data of 453 oncological patients with available manually generated ground-truth segmentations. Quantitative segmentation performance was assessed for the different CAM approaches and compared with the manual ground truth segmentation and with supervised segmentation methods. In addition, further biomarkers (MTV and TLG) were extracted from the segmentation masks. Results: A weakly supervised segmentation of tumor lesions was feasible with satisfactory performance [best median Dice score 0.47, interquartile range (IQR) 0.35] compared with a fully supervised U-Net model (median Dice score 0.72, IQR 0.36) and a simple threshold based segmentation (Dice score 0.29, IQR 0.28). CAM, GradCAM++, and ScoreCAM yielded similar results. However, GradCAM led to inferior results (median Dice score: 0.12, IQR 0.21) and was likely to ignore multiple instances within a given slice. CAM, GradCAM++, and ScoreCAM yielded accurate estimates of metabolic tumor volume (MTV) and tumor lesion glycolysis. Again, worse results were observed for GradCAM. Conclusions: This work demonstrated the feasibility of weakly supervised segmentation of tumor lesions and accurate estimation of derived metrics such as MTV and tumor lesion glycolysis.

Novel mesh-derived right ventricular free wall longitudinal strain analysis by intraoperative three-dimensional transoesophageal speckle-tracking echocardiography: a comparison with conventional parameters.

Longitudinal right ventricular (RV) function is substantial and might be reflected by free wall longitudinal strain (FWLS). Software solutions for FWLS analysis by two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE) are available, but data on validation are sparse. In this study, a novel method for FWLS analysis on 3D meshes ("mesh surface", MS-FWLS,) was tested for feasibility and compared to available parameters. 80 patients undergoing left-sided cardiac valve surgery with intraoperative TEE were included retrospectively. 2D-FWLS, 3D-derived (3Dd)-FWLS (assessed in optimized four-chamber views after volume analysis) and MS-FWLS were measured and compared to conventional parameters (3Dd-TAPSE, FAC and RVEF). The mean FWLS values did not differ significantly between methods (- 19.0 ± 6.1%, - 20.0 ± 7.3%, - 19.5 ± 7.3% for 2D-, 3Dd- and MS-FWLS, respectively). No significant differences in the mean FWLS between patients with normal or increased pulmonary artery pressures as well as normal or reduced left ventricular ejection fraction were observed. Agreement was best between 3Dd- and MS-FWLS (r = 0.89, bias = - 1.0%, LOA ± 6.9%). Conventional echocardiographic parameters yielded poorer intermodality agreement. In patients with discrepant results between 2D- and 3Dd-FWLS, 3Dd-FWLS and MS-FWLS yielded similar results (r = 0.82, bias = - 0.3%, LOA ± 8.6%), while 2D-FWLS and MS-FWLS did not. Intra- and interobserver variabilities of strain analyses were low. MS-FWLS might represent a promising method to overcome artefacts associated with 2D analysis. Its prognostic relevance needs to be investigated in prospective studies.

Regional Right Ventricular Volume and Function Analysis Using Intraoperative 3-Dimensional Echocardiography-Derived Mesh Models.

OBJECTIVES: In daily echocardiographic practice, the right ventricle (RV) is assessed using mostly 2-dimensional (2D) echocardiography. Parameters measuring longitudinal shortening (eg, tricuspid annular plane systolic excursion) or changes in areas (eg, fractional area change) are used as surrogates for right ventricular function. Three-dimensional (3D) echocardiography-based techniques allow for cardiac magnetic resonance imaging-validated assessment of the RV. Depiction of regional right ventricular function is of increasing clinical interest. This study aimed to calculate regional volumetric changes in the right ventricular inlet, apical section, and outflow tract. Correlations between traditional parameters and regional right ventricular function were studied. DESIGN: Retrospective cohort study on patients scheduled for cardiac surgery. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 80 patients scheduled for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Based on 3D echocardiographic datasets, mesh models of the RV were generated on a vendor-independent platform. The meshes were further cut into the following 3 regions: the inlet part, the apical section, and the outflow tract. The regional volumes and ejection fractions were compared with the global right ventricular and left ventricular functions. Regional volumes were correlated linearly with the global end-diastolic volume. The right ventricular outflow tract demonstrated a significantly lower ejection fraction than the inlet part (34% ± 11% v 28% ± 11%; p = 0.0054). The function in the right ventricular outflow tract was reduced significantly compared with the global right ventricular function in patients with severely reduced left ventricular ejection fraction (<20%). CONCLUSION: The different parts of the RV seem to have different ejection fractions. Different regions of the RV are affected differently by reduced left ventricular ejection fraction. Regional right ventricular analyses could help clinicians better understand pathologic states of the RV.

Diffuse leukoencephalopathy and brain edema: unusual presentations of CNS relapse of acute myeloid leukemia.

An isolated CNS relapse is rarely seen in acute myeloid leukemia. However, it has a potentially fatal clinical outcome. We herein present the case of a 39-year-old man, who presented to our emergency room with horizontal diplopic images, vertigo, bilateral deafness, and progressing somnolence. Cerebral imaging revealed cerebral and cerebellar edema and a diffuse leukoencephalopathy. With the one-year-old history of an initially successfully treated FAB-M0 acute myeloid leukemia (AML) in mind, a lumbar puncture was carried out that showed a vast number of myeloid blasts in the morphologic analysis of the cerebrospinal fluid. In conjunction with normal findings in the peripheral blood-count with differential and the bone marrow examination a diagnosis of an isolated CNS relapse of the AML was made. Cytarabine chemotherapy was initiated and the symptoms resolved rapidly. To our surprise, cerebral imaging in the course of the treatment not only showed a resolution of the brain edema but also of the leukoencephalopathy, pointing to a direct infiltration of brain parenchyma by leukemic blasts. The case highlights the relevance of the CNS as a pharmacologic "sanctuary" for tumor cells in patients that on prior treatments have not received intrathecal chemotherapy or chemotherapeutics that cross the blood-brain barrier.

Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques.

OBJECT: The use of dural grafts is frequently unavoidable when tension-free dural closure cannot be achieved following neurosurgical procedures or trauma. Biodegradable collagen matrices serve as a scaffold for the regrowth of natural tissue and require no suturing. The aim of this study was to investigate the efficacy and safety of dural repair with a collagen matrix using different fixation techniques. METHODS: A total of 221 patients (98 male and 123 female; mean age 55.6 +/- 17.8 years) undergoing cranial (86.4%) or spinal (13.6%) procedures with the use of a collagen matrix dural graft were included in this retrospective study. The indications for use, fixation techniques, and associated complications were recorded. RESULTS: There were no complications of the dural graft in spinal use. Five (2.6%) of 191 patients undergoing cranial procedures developed infections, 3 of which (1.6%) were deep infections requiring surgical revision. There was no statistically significant relationship between the operative field status before surgery and the occurrence of a postoperative wound infection (p = 0.684). In the 191 patients undergoing a cranial procedure, cerebrospinal fluid (CSF) collection occurred in 5 patients (2.6%) and a CSF fistula in 5 (2.6%), 3 of whom (1.6%) required surgical revision. No patient who underwent an operation with preexisting CSF leakage had postoperative CSF leakage. Postoperative infection significantly increased the risk for postoperative CSF leakage. The collagen matrix was used without additional fixation in 124 patients (56.1%), with single fixation in 55 (24.9%), and with multiple fixations in 42 (19%). There were no systemic allergic reactions or local skin changes. Follow-up imaging in 112 patients (50.7%) revealed no evidence of any adverse reaction to the collagen graft. CONCLUSIONS: The collagen matrix is an effective and safe cranial and spinal dural substitute that can be used even in cases of an existing local infection. Postoperative deep infection increases the risk for CSF leakage.

Radiologic morphology of low-grade primary central nervous system lymphoma in immunocompetent patients.

BACKGROUND AND PURPOSE: Primary central nervous system lymphomas (PCNSLs) are usually high-grade and are rarely low-grade non-Hodgkin lymphomas (NHLs). On MR imaging, PCNSLs typically present as contrast-enhancing lesions in contact with the subarachnoid space without evidence of necrosis. We evaluated the radiologic morphology and clinical characteristics of low-grade PCNSLs, hypothesizing that they may differ from high-grade PCNSLs. METHODS: Records were reviewed from 332 patients screened for inclusion in 3 multicenter prospective trials. MR imaging scans were obtained from all patients and were centrally reviewed by 2 consultant neuroradiologists. RESULTS: Ten patients (3%) with low-grade PCNSLs (7 men and 3 women; median age, 59 years; age range, 19-61 years) were identified. Four patients had one lesion, 2 patients 2 lesions, and 4 patients had multiple lesions. The following radiologic features infrequently seen in high-grade PCNSLs were found in a substantial proportion of patients: location in deep structures or spine (n = 6); lack of periventricular location (n = 5); hyperintensity on T2-weighted images (n = 10); moderate or absent contrast enhancement (n = 6); and heterogeneous contrast enhancement (n = 5). In 8 patients, >2 of these features were present in at least one lesion, and, thus, the radiologic appearance was assessed atypical of high-grade PCNSLs. The atypical radiologic appearance in combination with atypical or mild symptoms resulted in a false or delayed diagnosis. CONCLUSION: Low-grade PCNSLs may have a variable and atypical radiologic morphology compared with high-grade PCNSLs with the risk of false or delayed diagnosis.

Low-grade primary central nervous system lymphoma in immunocompetent patients.

Primary central nervous system lymphomas (PCNSL) are usually diffuse large B-cell non-Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation, course and outcome of patients with low-grade PCNSL. Records of 332 patients screened for inclusion in three multicentre prospective trials were reviewed. Ten patients (3%) with a median age of 59 years and a median Karnofsky performance status of 70% were identified. Seven patients had B-cell and three had T-cell lymphoma. The median growth fraction was 4%. The radiological morphology was unusual for PCNSL in eight patients. Three patients underwent complete tumour resection, combined with chemotherapy in one patient and with chemotherapy plus local radiotherapy in another. Four patients received chemotherapy and three received chemotherapy plus whole-brain irradiation, resulting in four complete remissions, two no-change situations and one progressive disease. Patients had an overall survival (OAS) of 2-58+ months with a 2-year OAS of 67%. Low-grade PCNSL may differ from classical high-grade PCNSL in its clinical features and radiological morphology. The clinical course may be variable and frequently more indolent than in classical PCNSL.

Treatment of glioblastoma with intravenous taurolidine. First clinical experience.

BACKGROUND: Despite progress in diagnosis and therapy, the prognosis of patients with glioblastoma remains poor. Recently it has been found that the antibacterial agent taurolidine has a direct and selective antineoplastic effect on brain tumor cells by the induction of programmed cell death. This paper reports on intravenous taurolidine treatment in two patients with a progressive glioblastoma despite conventional therapy. PATIENTS AND METHODS: Two male patients with histopathologically diagnosed glioblastoma were included. The tumors were progressive despite conventional therapy. Intravenous taurolidine treatment was initiated. RESULTS: The neurological condition and quality of life improved in both patients such that they could be discharged for further outpatient treatment. Follow-up demonstrated partial remission of the tumor in both patients. However, both patients died about 4 months following the start of taurolidine treatment, from pneumonia and acute thrombembolism, respectively. CONCLUSION: Both patients achieved a transient, marked improvement in quality of life and partial tumor remission. There was a clear response to the taurolidine treatment.

N-acetylcysteine decreases lactate signal intensities in liver tissue and improves liver function in septic shock patients, as shown by magnetic resonance spectroscopy: extended case report.

BACKGROUND: N-acetylcysteine (NAC) has been shown to improve splanchnic blood flow in experimental studies. This report evaluates the effects of NAC on liver perfusion and lactate signal intensities in the liver tissue of septic shock patients using proton magnetic resonance imaging and spectroscopy. Furthermore, the monoethylglycinexylidide (MEGX) test was used to investigate hepatic function. METHODS: Five septic shock patients received 150 mg/kg body weight NAC as an intravenous bolus injection over 15 min. Lidocaine was injected both prior to and following NAC administration in order to determine MEGX formation. Measurements (hemodynamics, oxygen transport-related variables, blood samples for lactate, liver-related markers) were performed 1 hour before and 1 hour after NAC injection. In addition to the proton magnetic resonance imaging patients received two proton magnetic resonance spectra, one prior to and one 30 min subsequent to the onset of the NAC infusion at a 1.5 Tesla clinical scanner, for measurement of liver perfusion and liver lactate signal intensity. MAIN FINDINGS: Following NAC infusion, the lactate signal intensity in the liver tissue showed a median decrease of 89% (11-99%), there was a median increase in liver perfusion of 41% (-14 to 559%), and the MEGX serum concentration increased three times (1.52-5.91). CONCLUSIONS: A decrease in the lactate signal intensity in the liver tissue and an increase in the MEGX serum concentration and in liver perfusion might indicate improved liver function as a result of NAC administration. Patients with compromised hepatosplanchnic function, such as patients with septic shock due to peritonitis, may therefore benefit from NAC therapy.

Cerebrovascular reactivity in major depression: a pilot study.

OBJECTIVE: There are a growing number of reports that depression may increase the risk of stroke. Little is known, however, about the pathophysiologic mechanisms underlying this association. Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism to provide constant cerebral blood flow. We hypothesized that CVR is reduced in patients with major depression, thus contributing to the association between depression and stroke. METHODS: We assessed CVR in 33 patients with unipolar depression and 26 healthy controls by calculating the increase in cerebral blood flow velocity after stimulation with acetazolamide. Blood flow velocities were measured by transcranial Doppler ultrasound. RESULTS: Cerebrovascular reactivity was significantly reduced in depressed patients. Smoking was also associated with a significant reduction in CVR, whereas age and gender had no significant influence. CONCLUSIONS: Cerebrovascular reactivity appears to be impaired in major depression. Further studies should clarify the mechanisms leading to this reduced CVR.

Laser induced thermotherapy (LITT) of experimental liver metastasis-detection of residual tumors using Gd-DTPA enhanced MRI.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the accuracy of Gd-DTPA MRI in the detection of recurrent tumor after laserinduced thermotherapy (LITT) of experimental liver metastases. STUDY DESIGN/MATERIALS AND METHODS: LITT was performed at different energy levels in VX-2 tumor-bearing rabbits (n = 80). MRI and histology were placed at 0, 24, 96 hours, and 14 days. Signal intensities were calculated of the transition between thermally damaged and undamaged tissue (transition zone = TZ) and of the surrounding tissue (reference zone = RZ). RESULTS: Tumor recurrence was seen in 47 animals. At 24 hours sensitivity, specificity and accuracy was 92, 100, and 95% in TZ and 23, 100, and 50% in RZ. At 14 days sensitivity, specificity and accuracy was 100, 11, and 60% in TZ and 100, 89, and 95% in RZ. CONCLUSIONS: Recurrence is best excluded in TZ at 24 hour and in RZ at 14 day with an accuracy up to 95%.