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Programmable ultrasound imaging using multimedia technologies: a next-generation ultrasound machine.

High computational and throughput requirements in modern ultrasound machines have restricted their internal design to algorithm-specific hardware with limited programmability. We have architected a programmable ultrasound processing system, Programmable Ultrasound Image Processor (PUIP), to facilitate engineering and clinical ultrasound innovations. Multiple high-performance multimedia processors were used to provide a computing power of 4 billion operations per second. Flexibility was achieved by making our system programmable and multimodal, e.g., B-mode, color flow, cine and Doppler data can be processed. We have successfully designed and implemented the PUIP to fit within an ultrasound machine. It provides a platform for rapid testing of new concepts in ultrasound processing and enables software upgrades for future technologies. Current and future clinical applications include extended fields of view, quantitative measurements, three-dimensional ultrasound reconstruction and visualization, adaptive persistence, speckle reduction, edge enhancement, image segmentation, and motion analysis. The PUIP is a significant step in the evolution of ultrasound machines toward more flexible and generalized systems bridging the gap between many innovative ideas and their clinical use in ultrasound machines.

Algorithms↗

Long term follow up after perimesencephalic subarachnoid haemorrhage.

OBJECTIVES: To evaluate the long term sequelae of perimesencephalic subarachnoid haemorrhage (PMSAH). METHODS: Twenty one consecutive patients were studied. All patients were examined by CT, angiography, MRI, multimodal evoked potentials, and transcranial Doppler sonography. All relevant clinical data during hospital stay and outcome at discharge were obtained by reviewing the charts. Long term follow up was evaluated by reviewing the outpatient files and dedicated outpatient review. Patients were specifically questioned about their perceived recovery, residual complaints, and present occupational status. RESULTS: Apart from the initial CT confirming the diagnosis of PMSAH all other examinations disclosed no abnormalities. None of the patients developed any complications during hospital stay, and all patients were discharged in good clinical condition and without neurological deficits. At long term follow up 62% of the patients had residual complaints consisting of headaches, irritability, depression, forgetfulness, weariness, and diminished endurance. Apart from four patients who had already retired before the PMSAH, only seven of the remaining 17 patients (41%) returned to their previous occupation, whereas nine patients (53%) retired from work and one man became unemployed. One patient had a recurrence of PMSAH 31 months after the first event. CONCLUSION: PMSAH can have considerable long term psychosocial sequelae, and may also recur. Prognosis may not be as good as previously reported.

Adult↗

Neoadjuvant radio-chemotherapy of adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Recently, neoadjuvant radio-chemotherapy has been demonstrated to induce tumour remission and to prolong survival of patients with locally advanced adenocarcinoma of the oesophagogastric junction.The present study was performed to re-evaluate these data. PATIENTS AND METHOD: A non-randomised trial of multimodal treatment was conducted in order to investigate histopathologic response and survival of patients with adenocarcinoma of the oesophagogastric junction. Treatment consisted of 2 courses of combined chemotherapy with 15 mg/kg 5-fluorouracil on days 1-5 and 75 mg/m(2) cisplatin on day 8 and simultaneous radiation (40 Gy), and a second course starting on day 36, followed by surgery. Abdomino-thoracic oesophagectomy and systematic 2-field lymphadenectomy were performed in patients with Barrett's carcinoma. D2-gastrectomy was performed in patients with type 2 or 3 cancer of the oesophagogastric junction according to the Siewert classification. Probability of survival was estimated using the Kaplan-Meier method. RESULTS: 16 patients with a mean age of 57 years were enrolled in this study. Surgery was performed in 14 of these patients. Response to treatment was evident in 10 patients, but none of these patients had complete histopathologic response. Toxicity related to radiochemotherapy was mild to moderate (37.5%). Perioperative complications, both medical and surgical, occurred in 71.4% of patients. 2 patients had fatal complications. 30-day mortality was 25.4%. The probability of survival at 2 years after surgery was 61.2%. CONCLUSION: Neoadjuvant radio-chemotherapy followed by surgery for cancer of the oesophagogastric junction is associated with a considerable rate of complications. Histopathologic response to radio-chemotherapy is poor. In consequence of these preliminary results, the present study was terminated and the protocol of a future study was modified.

Adenocarcinoma↗

Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. METHODS: This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. CONCLUSIONS: The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.

Aged↗

Beyond Morphology: Reframing Lymph-Node Metastasis Prediction Through Clonal Ecology-Decades-Long Genomic Instability and Polyclonal-to-Monoclonal Transitions as the Missing Dimension in Cancer.

Recent whole-genome, lineage-tracing, single-cell, and spatial studies have reshaped our understanding of tumor evolution, revealing that cancers can arise from polyclonal populations, undergo decades-long genomic instability before clinical detection, and progress through dynamic changes in subclonal composition, cellular state, and ecological organization. These findings challenge the assumption underlying morphology-based prediction models that metastatic risk can be inferred from static histological features alone. Here, we revisit lymph-node metastasis prediction in colorectal cancer through clonal ecology, integrating computational pathology with evolutionary oncology. Drawing on the subclonal switchboard model proposed in 2012 and subsequent artificial intelligence (AI)-enabled approaches for tracking dominant and dormant subclones, we synthesize evidence that metastatic potential reflects clonal ancestry, evolutionary timing, spatial niche architecture, cellular plasticity, intercellular interactions, dormancy, and treatment-driven shifts in subclonal fitness. We define five complementary methodological pillars for operationalizing clonal ecology: single-cell transcriptomics for resolving rare subclones, evolutionary trajectories, and adaptive cell states; lineage tracing and phylogenetics for reconstructing clonal ancestry and divergence; spatial transcriptomics and genomics for mapping subclonal geography and tumor-stromal-immune interactions; longitudinal liquid biopsy surveillance for monitoring residual disease, clonal turnover, and emerging resistance; and AI-enabled multimodal integration for connecting histopathology, genomics, spatial biology, and longitudinal data into predictive ecological-state models. Multiple-instance learning and pathology foundation models provide scalable computational foundations for evolution-aware prediction. Translationally, dormant subclones represent actionable reservoirs of recurrence. A longitudinal clinical and experimental study of KMT2A-rearranged acute myeloid leukemia further supports central predictions of the subclonal switchboard framework by demonstrating treatment-associated shifts in subclonal dominance, persistence of cryptic adaptive programs, and ecological rewiring during resistance and relapse. We propose clonal ecology as a measurable dimension for extending morphology-driven prediction toward integrative models that anticipate evolutionary transitions, identify therapeutic windows, and proactively constrain adaptive tumor ecosystems before resistant or metastatic subclones achieve clinical dominance.

Humans↗

Pulse-height light-scatter distributions using flow-systems instrumentation.

Several laboratories have recently been making light-scatter measurements on cells and other particles using flow-systems instrumentation. We at the Los Alamos Scientific Laboratory, as well as others, have obtained multimodal pulse-height distributions in certain angular regimes from particles of supposedly uniform characteristics. Because it was assumed that multimodal distributions implied characteristics of multivalue, the accuracy of such data has been doubted. In the present work, pulse-height distributions anticipated on the basis of exact electromagnetic theory were calculated for particles of known characteristics. These calculated pulse-height distributions agree quite well with those obtained experimentally. Physical optics form the basis for the explanation of the complex pulse-height distributions obtained experimentally. However, the results of this study show that certain cautions are necessary in the interpretation of light-scatter data presented in this manner.

Autoanalysis↗

Tools for visualizing multidimensional images from living specimens.

Over the last 50 years modern cell biology has been driven by the development of powerful imaging techniques. In particular, new developments in light microscopy that provide the potential to image the dynamics of biological events have had significant impact. Optical sectioning techniques allow three-dimensional information to be obtained from living specimens noninvasively. When used with multimodal fluorescence microscopy, advanced optical sectioning techniques provide multidimensional image data that can reveal information not only about the changing cytoarchitecture of a cell but also about its physiology. These additional dimensions of information, although providing powerful tools, also pose significant visualization challenges to the investigator. Particularly in the current postgenomic era there is a greater need than ever for the development of effective tools for image visualization and management. In this review we discuss the visualization challenges presented by multidimensional imaging and describe three open-source software programs being developed to help address these challenges: ImageJ, the Open Microscopy Environment, and VisBio.

Animals↗

Multimodality management in severe pediatric spleen trauma.

BACKGROUND: Trauma is the leading cause of death in children. In abdominal lesions the spleen is the most commonly involved organ. During the last two decades much effort has focused on spleen tissue conservation. OBJECTIVES: To analyze the rationale of a multimodality management policy that includes autotransfusion and mesh wrapping. METHODS: Data gathered over 14 years illustrate the introduction of new techniques and their impact on cases of severe spleen rupture. RESULTS: A total of 122 children were treated during the 14 year period, 1985-98. In 16 children an absorbable mesh wrapping, alone or in combination with other techniques, was used to obtain hemostatis and save spleen tissue. CONCLUSIONS: Mesh wrapping, partial splenectomy and autotransfusion can be used, alone or in combination, to preserve severely injured spleens. According to our records, all children survived with a functional spleen. There were no cases of rebleeding. In only one case of prolonged postoperative fever could the cause be traced to an infected spleen hematoma that was drained transcutaneously. Autotransfusion is performed simply and without the use of a "cell saver." Its use can be crucial in small or field hospitals or in a situation of mass casualty.

Adolescent↗

Epidemiology, clinical features and treatment outcome of Wilms' tumor in Taiwan: a report from Taiwan Pediatric Oncology Group.

BACKGROUND AND PURPOSE: Taiwan Pediatric Oncology Group (TPOG)-W-91 is the first multi-institutional Wilms' tumor study for children in Taiwan. This clinical trial used a multidisciplinary approach, based on and similar to the National Wilms' Tumor Study 4. The study was conducted to evaluate the epidemiological characteristics and analyze the outcome of Wilms' tumor patients treated with this protocol. METHODS: Ninety eight children with Wilms' tumor (WT) were analyzed for distributions of age, gender, associated congenital anomalies, tumor sites, histology, tumor weights, and clinical stages. Patients received individualized multimodality treatment based upon the histology of the tumor and clinicopathologic stage. The treatment included surgery, radiotherapy and 2-, 3-, and 4-agent active chemotherapeutic agents. Seventy patients were eligible for analysis of treatment outcome. The endpoints were progression-free and overall survival (PFS, OS). Patients were divided into various subgroups according to the chemotherapy regimen used, tumor stage, age at diagnosis, gender, and tumor weight. The prognostic factors were evaluated and the survival rates of various clinical subgroups were compared using log-rank test. RESULTS: The average annual incidence rate of WT was 2.9 per million children under 15 years of age. The M/F ratio was 1.04. The mean age at diagnosis was 3.7 years. All bilateral tumors occurred in females. Congenital anomalies were present in 17.3% of patients. Anaplastic histology was found in 6 of 98 cases (6.1%). The stage distribution was: I, 43.2%; II, 19.3%; III, 23.9%; IV, 6.8%; and V, 6.8%. The median follow-up time was 89.1 months (range, 1.8 to 128.1 months). The 5-year PFS rate was 0.7841 (SE, 0.0494; 53 of 70 patients) and the 5-year OS rate was 0.886 (SE, 0.038; 63 of 70 patients). Gender was found to be the only significant prognostic variable. CONCLUSIONS: This study evaluated the epidemiological characteristics, clinical features, multimodality therapy regimens, and treatment outcome of WT in Taiwan. Data obtained from this study may lead to further improvement in the prognosis of pediatric malignant solid tumor.

Adolescent↗

Long-term survival in malignant glioma. Prognostic factors.

Mean survival of patients with malignant glioma is six months. Only 7.5% of these patients survive two years. We identified 14 patients, nine with glioblastoma multiforme and five with anaplastic astrocytoma, who survived more than two years. All were treated initially with surgery, radiation and adjuvant chemotherapy. One patient who received three years of nitrosourea has lived longer than 7.3 years. Seven of the 14 patients have no sign of tumor recurrence four years after diagnosis. Nine surviving patients were younger than 45 years of age at the time of diagnosis. Five died of tumor recurrence with the median survival time of 3.5 years. This data suggests that onset at a younger age (< 45 years), multimodality therapy, high Karnofsky Performance Scale and frontal lobe tumors were the major prognostic factors that contributed to long-term survival.

Adolescent↗

[The systematics of acute and chronic radiation sequelae].

A classification system in German language is proposed for scoring of acute and chronic treatment sequelae after radiotherapy. It includes all important organs and organ systems. The proposed grading corresponds to the four-scale-system of the WHO and UICC. The system is also compatible to the RTOG and EORTC acute and late radiation morbidity scoring criteria. This facilitates the data transfer for retrospective and prospective analysis of monomodal and multimodal radiotherapy treatment regimens. We recommend to use this scoring system in all German speaking countries for multicentric prospective studies. It is possible, that organ-specific sophistication of the toxicity grading will be developed in the future. These additions should conform with (inter)national standards and apply the same four-scale grading of this classification system.

Acute Disease↗

[The multimodal integration, correlation and fusion of morphology and function: the methods and initial clinical applications].

Besides the pure visual diagnosis of morphology in comparison with function, digital multimodal image analysis is steadily gaining in importance. Digital image processing is used in integration, correlation and fusion of topographically identical image data. After defining these terms and describing the acquisition techniques and influence parameters, this article reviews the methods of multimodal image processing, with emphasis on correlation methods. It also gives a short description of special methods in nuclear medicine. The clinical part briefly reviews the clinical use as well as the progress achieved and the benefits expected for diagnostic applications.

Diagnostic Imaging↗

Multimodal brain monitoring in the neurological intensive care unit: where does continuous EEG fit in?

Continuous EEG (cEEG) is a vital component of patient monitoring in the neurologic intensive care unit, allowing the intensivist to diagnose nonconvulsive seizure activity. Though still in its infancy, Fourier-transformed cEEG data are also increasingly being used in ICUs to monitor global cerebral activity and cortical function. In conjunction with other components of multimodality neurologic monitoring, including intracranial pressure, cerebral blood flow, brain tissue oxygen tension monitoring, transcranial Doppler, and microdialysis monitoring, cEEG provides unique data regarding the electrical activity of the brain. The main challenge for clinicians and researchers will be to understand how these different aspects of multimodality monitoring relate to each other, and how physiologic variables such as blood pressure, osmolality, and temperature can be manipulated to optimize cerebral function and tissue survival in the setting of acute injury.

Brain↗

Multimodal magnetic resonance imaging of the central nervous system.

The physiological and biochemical properties of the diseased brain that can be explored with magnetic resonance imaging (MRI) are increasing. Progress in MR-based technology affords a large panel of MRI sequences that explore different phenomena and, thus, provide complementary informations. The diagnostic accuracy of MRI is improved by the combination of all MR modalities. However, this abundance of data requires an efficient multiparametric analysis to fully achieve the goal of the multimodal strategy. We will discuss the potential impact of this advanced MRI analysis in the clinical management and the therapeutical strategies of the most common brain pathologies (intracranial tumors, multiple sclerosis, stroke, epilepsy and dementia). This non-invasive approach is of utmost importance since it already improves the diagnosis and the therapeutic choice in the management of several central nervous system diseases.

Central Nervous System Diseases↗

[Interventions for improvement of primary care in patients with low back pain: how effective are advice to primary care physicians on therapies and a multimodal therapy program arising out of cooperation of outpatient health care structures?].

BACKGROUND: Treatment for chronic low back pain in primary care has a poor-quality outcome. There is evidence that multimodal therapy is the most successful approach to its management. We tried to evaluate whether giving primary care physicians evidence-based recommendations on therapy of chronic back pain or directly implementing a multimodal program would improve the outcome of patients with low back pain treated in primary care. METHODS: In the first phase, physicians were asked to document the course of patients suffering from low back pain of at least 4 weeks' duration with no decrease in intensity, noting pain intensity before and after 6 months of conventional, nonsurgical treatments. In the present, second, phase of the study, recommendations issued by the Medicines Committee of the German Medical Profession and the U.S. Agency for Health Care Policy and Research for the management of back pain were presented to doctors in printed form and at conferences. In parallel with this, a multimodal program for the treatment of chronic low back pain (4 h/day for 20 days: medical training therapy, cognitive-behavioral therapy, physiotherapy, and patient education) was organized in a private health-oriented sports center in cooperation with three private physiotherapy practices, and a psychologist and a pain specialist from the outpatient pain clinic at the University Hospital in Erlangen. We examined how physicians changed the therapy and how effective it was, the latter as reflected in the mean sum value of the percent pre- to posttreatment changes in pain intensity, how much pain interfered with daily living, depressivity, and quality of life. Data after interventions were compared with baseline data from the first phase. RESULTS: Data relating to 36 patients following treatment by 14 primary care physicians who had been given information about therapy recommendations and to 51 patients who had participated in the multimodal therapy program were compared with baseline data recorded in 157 patients. Recommendations changed neither the therapy preferred by primary care physicians nor the quality of outcome of conventional treatment. In contrast, the multimodal program of therapy for chronic low back pain improved the outcome significantly more than conventional therapy (mean improvement in general outcome score 22 vs. 7%, respectively, compared with baseline data; P<0.001). CONCLUSIONS: Giving primary care physicians information on the therapy recommended for treatment of low back pain does not lead to any change in physicians' preferred therapy. Multimodal programs for treatment of chronic low back pain should be organized locally, with existing health care providers joining forces to improve the quality of outcome in chronic low back pain managed in primary care.

Adult↗

Cell kinetics and multimodal prognostic evaluation in glial tumours investigated by serial stereotactic biopsy.

A retrospective evaluation of the prognostic value of different parameters available in patients affected by glial tumours and submitted to serial stereotactic biopsy is presented. The series investigated includes thirty-three untreated patients with proven brain gliomas submitted to stereotactic biopsy. All patients have been clinically and neuroradiologically monitored for three years. The factors investigated belong either to the preoperative data (clinical history and symptomatology, CT pattern and volume of the lesion) or to histological and biological data obtained after the stereotactic biopsy. The results suggest the need of a multimodal prognostic evaluation in glial tumours and particularly stressed is the accuracy of prognostic indications derived from cell kinetic studies.

Adult↗

Results of a multimodal treatment program for patients with chronic symptoms after a whiplash injury of the neck.

STUDY DESIGN: A descriptive case series pre- and post-treatment design, including a 6-month follow-up. OBJECTIVES: The objective of this study was to document the improvements of patients with chronic symptoms after a "whiplash" injury of the neck, who attended a 4-week multimodal treatment program at the Rug AdviesCentra Nederland. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, no studies have been conducted on the effectiveness of multidisciplinary treatment of chronic symptoms after whiplash injury. METHODS: Twenty-six patients who experienced Quebec type 1 or 2 lesions of the neck (whiplash) with persisting symptoms of longer than 6 months' duration participated in the study. The measures included were pain intensity (according to the visual analog scale), number of painful sites (determined by pain drawing), self-reported disability Quebec Back Pain Disability Scale; and symptoms of somatic and psychological distress and cognitive symptoms (according to selected Minnesota Multiphasic Personality Inventory-2 scales). Furthermore, objective outcome criteria were used regarding return to work, medication, and medical and paramedical treatment. Statistical and clinical significance of treatment results were both assessed. RESULTS: The patients' symptoms improved significantly on nearly all self-report measures. Their scores for objective outcome criteria reported during the 6-month follow-up evaluation were: complete return to work (65%); complete or partial return to work (92%); no use of analgesics in the past 6 months (58%); and no medical or paramedical treatments in the past 6 months (81%). CONCLUSION: These early results indicate that a multimodal treatment program has the potential to be an effective treatment for patients with chronic symptoms after a whiplash injury of the neck--a group of patients who have in the past been considered intractable or, at the very least, puzzling.

Activities of Daily Living↗

[Multimodality treatment of malignant brain tumors].

The outcome of treatment for malignant brain tumors has remarkably improved in recent years by applying multimodal therapeutic procedures. This conclusion was made by analysis of accurate data consisting 22,600 cases of completely followed brain tumor patients accumulated under the All Japan Brain Tumor Registry. The 5-years survival rates of malignant brain tumors have much improved in these 15 years, in which the most significant improvements were noticed in cases of medulloblastoma and intracranial germ cell tumors. The 5-year survival rate of medulloblastoma was improved from about 30% to more than 80%, and the number of cured patients are increasing. These favorable results are due to many factors, such as advanced imaging diagnosis of CT scan and MRI, radical surgical removal of tumors under operating microscope, and combined radiotherapy with chemotherapy. The synchronized chemoradiotherapy using vincristine and ACNU or ACNU and interferon has significantly improved the outcome of treatment for malignant gliomas. The administration of calcium entry blocker before the injection of vincristine has improved the effectiveness rates of chemoradiotherapy. Germinoma can completely be cured by chemoradiotherapy. The 5-year survival rates of germinoma have reached to 100% in female and more than 93% in male cases. The effectiveness of surgical removal, sensitivity for radiotherapy and chemotherapy were analyzed in various histological types of brain tumors and the significant effect of multimodal treatment for these tumors were discussed.

Brain Neoplasms↗