Joint reconstruction and segmentation in undersampled 3D knee MRI combining shape knowledge and deep learning.

Objective.Task-adapted image reconstruction methods using end-to-end trainable neural networks (NNs) have been proposed to optimize reconstruction for subsequent processing tasks, such as segmentation. However, their training typically requires considerable hardware resources and thus, only relatively simple building blocks, e.g. U-Nets, are typically used, which, albeit powerful, do not integrate model-specific knowledge.Approach.In this work, we extend an end-to-end trainable task-adapted image reconstruction method for a clinically realistic reconstruction and segmentation problem of bone and cartilage in 3D knee MRI by incorporating statistical shape models (SSMs). The SSMs model the prior information and help to regularize the segmentation maps as a final post-processing step. We compare the proposed method to a simultaneous multitask learning approach for image reconstruction and segmentation (MTL) and to a complex SSMs-informed segmentation pipeline (SIS).Main results.Our experiments show that the combination of joint end-to-end training and SSMs to further regularize the segmentation maps obtained by MTL highly improves the results, especially in terms of mean and maximal surface errors. In particular, we achieve the segmentation quality of SIS and, at the same time, a substantial model reduction that yields a five-fold decimation in model parameters and a computational speedup of an order of magnitude.Significance.Remarkably, even for undersampling factors of up toR= 8, the obtained segmentation maps are of comparable quality to those obtained by SIS from ground-truth images.

Ground-truth-free deep learning for artefacts reduction in 2D radial cardiac cine MRI using a synthetically generated dataset.

In this work, we consider the task of image reconstruction in 2D radial cardiac cine MRI using deep learning (DL)-based regularization. As the regularization is achieved by employing an image-prior predicted by a pre-trained convolutional neural network (CNN), the quality of the image-prior is of essential importance. The achievable performance of any DL-based method is limited by the amount and the quality of the available training data. For fast dynamic processes, obtaining good-quality MR data is challenging because of technical and physiological reasons. In this work, we try to overcome these problems by a transfer-learning approach which is motivated by a previously presented DL-method (XT,YT U-Net). There, instead of training the network on the whole 2D dynamic images, it is trained on 2D spatio-temporal profiles (xt,yt-slices) which show the temporal changes of the imaged object. Therefore, for the training and test data, it is more important that their spatio-temporal profiles share similar local features rather than being images of the same anatomy. This allows us to equip arbitrary data with simulated motion that resembles the cardiac motion and use it as training data. By doing so, it is possible to train a CNN which is applicable to cardiac cine MR data without using ground-truth cine MR images for training. We demonstrate that combining XT,YT U-Net with the proposed transfer-learning strategy delivers comparable performance to CNNs trained on cardiac cine MR images and in some cases even qualitatively surpasses these. Additionally, the transfer-learning strategy was investigated for a 2D and 3D U-Net. The images processed by the the CNNs were used as image-priors in the CNN-regularized iterative reconstruction. The XT,YT U-Net yielded visibly better results than the 2D U-Net and slightly better results than the 3D U-Net when used in combination with the presented transfer learning-strategy.

Neural networks-based regularization for large-scale medical image reconstruction.

In this paper we present a generalized Deep Learning-based approach for solving ill-posed large-scale inverse problems occuring in medical image reconstruction. Recently, Deep Learning methods using iterative neural networks (NNs) and cascaded NNs have been reported to achieve state-of-the-art results with respect to various quantitative quality measures as PSNR, NRMSE and SSIM across different imaging modalities. However, the fact that these approaches employ the application of the forward and adjoint operators repeatedly in the network architecture requires the network to process the whole images or volumes at once, which for some applications is computationally infeasible. In this work, we follow a different reconstruction strategy by strictly separating the application of the NN, the regularization of the solution and the consistency with the measured data. The regularization is given in the form of an image prior obtained by the output of a previously trained NN which is used in a Tikhonov regularization framework. By doing so, more complex and sophisticated network architectures can be used for the removal of the artefacts or noise than it is usually the case in iterative NNs. Due to the large scale of the considered problems and the resulting computational complexity of the employed networks, the priors are obtained by processing the images or volumes as patches or slices. We evaluated the method for the cases of 3D cone-beam low dose CT and undersampled 2D radial cine MRI and compared it to a total variation-minimization-based reconstruction algorithm as well as to a method with regularization based on learned overcomplete dictionaries. The proposed method outperformed all the reported methods with respect to all chosen quantitative measures and further accelerates the regularization step in the reconstruction by several orders of magnitude.

Sequence and organization of the human vitamin D-binding protein gene.

The structure and organization of the human vitamin D-binding protein (DBP) gene has been determined. The gene is composed of 13 exons and 12 intervening sequences. With the help of the polymerase chain reaction (PCR) introns were amplified using exon-specific oligonucleotide primers, and were sequenced after subcloning; the exon/intron borders were determined. The introns 2, 5, 7, 9 and 10 were sequenced completely; the introns 1, 3, 4, 6, 8, 11 and 12 were sequenced in part. We designed intron-specific primers for the amplification of each exon by the PCR-method. This permits the analysis of mutational and function-related sites. By comparison with the genes for human albumin and alpha-fetoprotein the gene for DBP/GC is confirmed as a member of this multigene family. The location of the introns in the coding region of the human DBP-gene is identical with the position of the introns in the rat DBP-gene.

DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy.

Long acting somatostatin-14 (SST) analogs are used clinically to inhibit tumor growth and proliferation of various tumor types via binding to specific receptors (R). We have developed a 111In-/90Y-labeled SST analog, DOTA-(D)betaNal1-lanreotide (DOTALAN), for tumor diagnosis and therapy. 111In-/90Y-DOTALAN bound with high affinity (dissociation constant, Kd, 1-12 nM) to a number of primary human tumors (n = 31) such as intestinal adenocarcinoma (n = 17; 150-4000 fmol/mg protein) or breast cancer (n = 4; 250-9000 fmol/mg protein). 111In-/90Y-DOTALAN exhibited a similar high binding affinity (Kd, 1-15 nM) for the human breast cancer cell lines T47D and ZR75-1, the prostate cancer cell lines PC3 and DU145, the colonic adenocarcinoma cell line HT29, the pancreatic adenocarcinoma cell line PANC1, and the melanoma cell line 518A2. When expressed in COS7 cells, 111In-DOTALAN bound with high affinity to hsst2 (Kd, 4.3 nM), hsst3 (Kd, 5.1 nM), hsst4 (Kd, 3.8 nM), and hsst5 (Kd, 10 nM) and with lower affinity to hsst1 (Kd, approximately 200 nM). The rank order of displacement of [125I]Tyr11-SST binding to hsst1 was: SST (IC50, 0.5 nM) >> DOTALAN (IC50, 154 nM) > lanreotide (LAN) approximate to Tyr3-octreotide (TOCT) approximate to DOTA-Tyr3-octreotide (DOTATOCT) approximate to DOTA-vapreotide (DOTAVAP; IC50, >1000 nM); that to hsst2 was: DOTATOCT approximate to TOCT approximate to DOTALAN approximate to SST approximately LAN approximate to DOTAVAP (IC50, 1.4 nM); that to hsst3 was: SST (IC50, 1.2 nM) > DOTALAN = LAN (IC50, 15 nM) approximate to TOCT (IC50, 20 nM) approximate to DOTAVAP (IC50, 28 nM) > DOTATOCT (IC50, 73 nM); that to hsst4 was: SST (IC50, 1.8 nM) approximate to DOTALAN (IC50, 2.5 nM) > LAN (IC50, 22 nM) >> DOTATOCT approximate to DOTAVAP approximate to TOCT (IC50, >500 nM); and that to hsst5 was: DOTALAN (IC50, 0.45 nM) > SST (IC50, 0.9 nM) > TOCT (IC50, 1.5 nM) > DOTAVAP (IC50, 5.4 nM) >> LAN (IC50, 21 nM) > DOTATOCT (IC50 260 nM). In Sprague Dawley rats (n = 10), 90Y-DOTALAN was rapidly cleared from the circulation and concentrated in hsst-positive tissues such as pancreas or pituitary. Taken together, our results indicate that 111In-/90Y-DOTALAN binds to a broad range of primary human tumors and tumor cell lines, probably via binding to hsst2-5. We conclude that this radiolabeled peptide can be used for hsst-mediated diagnosis (111In-DOTALAN) as well as systemic radiotherapy (90Y-DOTALAN) of human tumors.

Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus.

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia.

Glucocorticoid (GC) resistance is a phenomenon of major significance in a number of clinical situations, including the therapy of lymphoid malignancies. Resistance may concern all, or just selected, GC effects, it may be absolute or just reflect a state of reduced sensitivity and, clinically relevant, be reversible or irreversible. Numerous molecular mechanisms can be envisaged acting either 'upstream' in the GC-triggered signaling pathway, i.e. at the level of the GC receptor (GR), or 'downstream' at the level of the GC-regulated genes responsible for individual GC effects. In lymphoid malignancies, GCs have anti-leukemic effects through the induction of apoptosis and/or cell cycle arrest. In this condition evidence for only a small number of mechanisms for GC resistance has been provided, mostly at the level of the GR. Herein, we review reports and hypotheses regarding 'upstream' and 'downstream' mechanisms for GC resistance in lymphoblastic leukemia and present an in vitro GC resistance model that might allow identification of resistance mechanisms.

Evidence for the existence of galanin receptors on cultured astrocytes of rat CNS: colocalization with cholinergic receptors.

The cellular localization of binding sites for [125I]galanin was studied in explant cultures of rat neocortex, cerebellum, locus coeruleus and spinal cord by means by of autoradiography. Binding sites for the peptide were observed on a great number of astrocytes in all CNS regions studied. In addition to astrocytes, many neurones were intensely labelled by [125I]galanin. Binding of [125I]galanin (10(-8) M) to both astrocytes and neurones was markedly reduced or inhibited by the unlabelled peptide at high concentration (10(-6) M), suggesting 'specific' binding of the radioligand. Evidence for the colocalization of galanin and cholinergic receptors on astrocytes was provided by combined autoradiographic and immunohistochemical studies. Many astrocytes were labelled by [125I]galanin and immunostained with antibodies to either muscarinic or nicotinic receptors. Electrophysiological studies revealed that addition of galanin (10(-9) to 10(-7) M) to the bathing fluid caused a dose-dependent hyperpolarization of the majority of astrocytes studied. When galanin (10(-8) M) and the cholinergic agonists muscarine and nicotine (10(-6) M) were tested on the same astrocyte, all three compounds induced a hyperpolarization, suggesting a colocalization of functional galanin and cholinergic receptors on the glial membrane.

Craniectomy in severe, life-threatening encephalitis: a report on outcome and long-term prognosis of four cases.

OBJECTIVE: To report the feasibility of craniectomy with duraplasty in four patients with life-threatening encephalitis and, in particular, their long-term outcome. DESIGN: Report of four cases, analysis of the acute clinical course and neurological long-term sequelae. RESULTS: Generous craniectomy with duraplasty was performed in four patients with life-threatening encephalitis leading to decortication and decerebration. This treatment approach reduced intracranial pressure. The long-term sequelae (1.5-8 years after craniectomy) confirmed its appropriateness, having led to full neurological (cerebral) function, resocialization, and reintegration into their professional life in all four patients. CONCLUSION: Craniectomy with dural augmentation is a treatment approach in cases of severe space-occupying encephalitis, not only saving the patient's life but also leading to favorable long-term outcome.

Rehabilitation of children after total correction of tetralogy of Fallot.

Nine children who had undergone total correction of tetralogy of Fallot were studied with the purpose of observing the physical changes that might be produced by a period of rehabilitation in hospital and comparing these results with those of a control group having the same pathology but which had not followed a protocol for physical activity. Precise criteria were used in the selection of the patients. Careful clinical examinations and exercise tests were conducted before and after the programme, in particular maximal stress testing on the bicycle ergometer and submaximal exercise on the treadmill. The sessions were held three times weekly in a gymnasium over three months, gradually increasing the duration of each session to a maximum of one hour. During the session, heart rate was monitored with a Sport-tester 3000 so as not to exceed 60%, then 70%, of the maximal heart rate recorded during the stress test. Testing at the end of the programme demonstrated an improvement in tolerance under maximal stress in 7 of the 9 patients. As for submaximal performance, 8 out of 9 children covered a greater distance using the same parameters as for initial testing. At the end of the programme, the children all showed increased independence and initiative and more self-confidence in establishing social relations. The programme has proven to be a comprehensive method for safely improving physical fitness in these patients and represents an important starting point for a better future.

Effects of normo- and hypocapnic nitrous-oxide-inhalation on cerebral blood flow velocity in patients with brain tumors.

Nitrous oxide (N2O) use during anesthesia for intracranial procedures has been a subject of controversy in the past. To date, the isolated influence of N2O on mean cerebral blood flow velocity in the middle cerebral artery (VMCA) has not been investigated during hypocapnia in patients with brain tumors. We compared VMCA during normocapnic (ETCO2: 40 mm Hg) and hypnocapnic (ETCO2: 25 mm Hg) inhalation of air and 50% nitrous oxide in oxygen N2O/O2 in eight patients with unilateral brain tumors on both the tumor side and the healthy side. Six patients completed the study. Mean VMCA increased during normocapnic inhalation of N2O/O2 (tumor side: 86 +/- 16 cm sec-1; healthy side: 74 +/- 17 cm sec-1) when compared with air (tumor side: 72 +/- 18 cm sec-1; healthy side: 62 +/- 14 cm sec-1, p < 0.01), whereas during hyperventilation VMCA decreased on both sides (p < 0.001). Mean VMCA values were quite similar during hypocapnic inhalation of 50% N2O/O2 (tumor side: 50 +/- 12 cm sec-1; healthy side: 45 +/- 13 cm sec-1) and air (tumor side: 51 +/- 14 cm sec-1; healthy side: 45 +/- 12 cm sec-1). The data of our study suggest that in patients with cerebral tumors the N2O-induced increase in mean VMCA can be completely reversed by hyperventilation.

Clinical and objective data on spinal cord stimulation for the treatment of severe Raynaud's phenomenon.

Ischemic vascular disease of the upper extremity represents a difficult therapeutic problem wherein medical treatment often fails. Epidural spinal cord stimulation has been shown to be an effective alternative in severe peripheral arterial disease. Although this method has been used for nearly two decades only limited experience exists in Raynaud's phenomenon of the upper limbs. In addition objective parameters to prove therapeutic success are not well defined. Herein we describe a patient with severe primary Raynaud's phenomenon over several years who had significant pain relief and complete healing of ischemic digital ulcerations after spinal cord stimulation. Pain level was evaluated using a visual rating scale before and after surgery. Microcirculatory parameters were assessed before and after spinal cord stimulation by capillary microscopy and laser Doppler anemometry. Significant improvement of red blood cell velocity, capillary density, and capillary permeability was demonstrated. At follow-up 18 months after surgery the patient had no complaints and all ulcerations of her fingertips had healed. Spinal cord stimulation appears to be an effective treatment in severe cases of Raynaud's phenomenon and we recommend its use in the case of failed medical therapy. Pain rating and capillary microscopy enable one to assess and visualize the effects of spinal cord stimulation.

Intrathecal baclofen application in patients with supraspinal spasticity secondary to severe traumatic brain injury.

Intrathecal application of baclofen is considered the treatment of choice in patients suffering from spinal spasticity insufficiently responding to conventional oral antispastic medication. This approach has also been used successfully in cases with spasticity of supraspinal origin. To achieve a good therapeutic response in the latter condition the amount of intrathecal baclofen has to be approximately twice the dosage required in spinal spasticity. We report on 8 patients suffering from supraspinal spasticity due to severe traumatic brain injury. Intrathecal baclofen reduced spasticity in all patients (mean Ashworth Score from 3.9 to 1.6; mean Reflex Score from 4.0 to 1.4). In some cases improvement of motor performance and in one case recovery of bladder function were noted. In two patients focal epileptic seizures with secondary generalization seemed to be associated with the application of baclofen. The local intrathecal application of baclofen has proven to be an effective therapy in otherwise intractable cases of severe supraspinal spasticity.

[Intraventricular morphine administration as a treatment possibility for patients with intractable pain]. / Intraventrikuläre Morphingaben als Behandlungsmöglichkeit bei Patienten mit nicht beherrschbaren Schmerzen.

The treatment of intractable pain, especially in cancer patients, often sets problems to patient and therapist. While epidural and intrathecal spinal administration of opiates is a routine treatment in pain with a sub-diaphragmatic topography it is almost ineffective in cervicocephalic or thoracic cancer. An alternative here is the administration of morphine into the lateral or third ventricle by a catheter-reservoir system. We report on our experience in the treatment of twenty patients, mostly suffering from cancer (18 cases), from 1990 to 1993. It is shown to be an effective, non-destructive method with minimal side effects in the treatment of nociceptive pain. Analgesia takes effect within a few minutes and the necessary doses are low. Our results agree with those of other authors describing good to excellent results in 95% of patients with somatogenic pain. However, no or only minimal effect is achieved in the treatment of neurogenic pain by intracerebroventricular morphine therapy.

[Retroperitoneal vascular injuries as a complication of lumbar disc operation]. / Retroperitoneal Gefässverletzungen als Komplikation von lumbalen Diskusoperationen.

We describe 2 cases of retroperitoneal hematoma after lumbar disc surgery following injury to retroperitoneal vessels. One patient sustained a partial tear of the right common iliac artery during left L4/5 discectomy, the other a complete tear of the lowest lumbar artery during left L5/S1 discectomy. Both patients developed hypovolemic shock 4-5 hours postoperatively, with acute abdominal symptoms and signs; the former patient also showed signs of ischemia of the right lower extremity. Both recovered completely after surgical intervention with vascular repair and evacuation of the retroperitoneal hematoma.

[Intraoperative radiotherapy of brain gliomas]. / Intraoperative Bestrahlung (IORT) von Hirngliomen.

11 patients with recurrent brain tumours underwent intraoperative radiotherapy (IORT) at a dosage of 15-25 Gy of fast electrons (17-20 MEV). IORT allows a higher dose of irradiation to be delivered to a well-defined target than is possible with external radiation, in anticipation of favourable results. However, tumour growth was not influenced in 7 out of the 11 patients and these patients died between 2 and 10 months following IORT. The remaining four patients are living still up to 15 months postoperatively. Due to the inhomogeneity of our patients no definitive conclusions can be drawn. However, well-defined tumours which can be radically excised are definitely more suitable for IORT than large, infiltrating tumours.

[On the topic of do not resuscitate (DNR) orders on intensive care units: an evaluation of the present status on intensive care units of the Innsbruck University clinics]. / Die Problematik des Do Not Resuscitate (DNR)-Vermerks an Intensivmedizinischen Stationen: Eine Evaluierung des Ist-Zustandes an den Intensivmedizinischen Abteilungen der Universitätskliniken Innsbruck.

INTRODUCTION: Intensive care physicians are frequently called upon to decide whether intensive care treatment is justified. Critically ill patients with a poor prognosis receive "Do Not Resuscitate (DNR) Orders", which entitles the physician in charge to withhold cardiopulmonary resuscitation in case of cardiac arrest. Guidelines concerning the implementation of DNR orders do not exist for Austrian intensive care units. The aim of this study was to evaluate the different practices of issuing a DNR order in the departments of intensive care medicine at the University Hospital of Innsbruck. METHODS: Forty-nine physicians working in intensive care units were interviewed about the different procedures in the management of a DNR order. Furthermore, the various answers of senior physicians and assistant physicians were evaluated. RESULTS: Thirty-nine per cent of the interviewed physicians reported that DNR orders were always issued in writing. According to the answers of 63% of intensive care physicians, the decision to issue a DNR order is usually made by senior physicians. Twenty-nine per cent mentioned that nurses are never included in the decision making process and 6%, that the family is not included in the decision making process. According to 29%, the family is regularly informed about a written DNR order. Twenty per cent of the interviewed physicians reported that the quality of the administration of a written DNR order is very good, 6% that the quality is poor. CONCLUSION: We believe that the unsatisfactory situation in regard of DNR orders is not due to inactivity on the part of physicians, but is more likely a result of the inconclusive and, in part, contradictory legal situation. The physician is compelled to take a major decision within a poorly defined legal situation.

[Implementing limited therapy methods in intensive care units: discontinuing therapy, reducing therapy and withholding therapy in intensive care units of the Innsbruck University Clinics]. / Durchführung therapielimitierender Massnahmen an Intensivmedizinischen Stationen: Therapieabbruch, Therapiereduktion und Therapieverzicht an den Intensivmedizinischen Abteilungen der Universitätskliniken Innsbruck.

INTRODUCTION: The intensive care physician is frequently confronted with the decision to withhold or withdraw therapy in patients with a poor prognosis. Apart from the legal implications, the practical management of withholding or withdrawing intensive care treatment continues to be indistinct. The subject has not been investigated in Austria or Germany. The aim of the study was to examine the different points of view of intensive care physicians and the various procedures to limit therapy in patients with a poor prognosis. METHODS: We interviewed physicians working at different intensive care departments of the University Hospital of Innsbruck from March to April 1998. RESULTS: Withholding treatment was given preference over withdrawing treatment. In regard of withdrawing treatment, 64% of the interviewed physicians felt more uncertain. In the decision making process the potential reversibility of disease was estimated to be more important than the wish of the patient. Hemofiltration and antibiotics were mentioned as the first measures the physicians would withdraw. The last measure that would be withheld was ventilatory support. Sixty-three per cent of the physicians felt that sedation and analgesia should be continued. In regard of withholding or withdrawing treatment 83% voted for an obligatory DNR order. CONCLUSION: Before withholding or withdrawing intensive care therapy, a medical specialist must determine and document the futile prognosis of the patient. If the patient's wish is unknown, all further decisions should be made in agreement with all participants. The goal of the therapy is to provide the patient maximum comfort under minimal intensive care treatment.

[Importance of intrathecal pain therapy]. / Stellenwert der intrathekalen Schmerztherapie.

Intraspinal drug infusion using implantable pumps and catheter systems is a safe and effective therapy for selected pain patients with severe chronic pain. It improves pain relief, reduces drug-related side effects, decreases the need for oral analgesia and enhances quality of life in a segment of chronic pain patients whose pain has not been controlled with more conservative therapies. Intrathecal drug therapy has therefore established its role in the treatment of malignant pain, benign pain and severe spasticity.Careful patient selection and management as well as a multidisciplinary approach are determinants of successful treatment. Current practices for patient selection and management, screening, drug selection, dosing and implantation for intrathecal drug delivery systems are discussed.