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Research-oriented image registry for multimodal image integration.

To provide multimodal biomedical images automatically, we constructed the research-oriented image registry, Data Delivery System (DDS). DDS was constructed on the campus local area network. Machines which generate images (imagers: DSA, ultrasound, PET, MRI, SPECT and CT) were connected to the campus LAN. Once a patient is registered, all his images are automatically picked up by DDS as they are generated, transferred through the gateway server to the intermediate server, and copied into the directory of the user who registered the patient. DDS informs the user through e-mail that new data have been generated and transferred. Data format is automatically converted into one which is chosen by the user. Data inactive for a certain period in the intermediate server are automatically achieved into the final and permanent data server based on compact disk. As a soft link is automatically generated through this step, a user has access to all (old or new) image data of the patient of his interest. As DDS runs with minimal maintenance, cost and time for data transfer are significantly saved. By making the complex process of data transfer and conversion invisible, DDS has made it easy for naive-to-computer researchers to concentrate on their biomedical interest.

Computer Communication Networks↗

[Multimodal evoked potentials in patients with dementia].

The event-related potential (ERP), somatosensory evoked potential (SEP) and visual evoked potential (VEP) were studied in 15 patients with Alzheimer's disease (AD), 16 patients with Parkinson's disease with dementia (PD), 7 patients with Binswanger's disease (BD) and 15 normal controls. ERP was recorded during auditory discriminative tasks. SEP evoked by median nerve stimulation was recorded from the second cervical vertebra and contralateral primary somatosensory cortex with a midfrontal reference. VEP was recorded during pattern reversal stimulation. All three groups with dementia showed significant prolongation of the N200 and P300 latencies of ERP compared with the normal controls. In addition, patients with AD showed significant prolongation of the P200 latency. There was a significant correlation between the P300 latency of ERP and MMSE scores in AD patients. Patients with AD and PD showed significant prolongation of the interpeak latency between N13 and P40 (N13-P40) and N20-P40 of SEP compared with the normal controls. Patients with BD showed significant prolongation of the N13-N20, N13-N33, N13-P40 and N20-P40. These results suggest that there is impairment of the ascending somatosensory pathway in patients with dementia. Patients with PD showed significant prolongation of the P100 latency of VEP compared with normal controls. There was a significant correlation between the N200 latency of ERP and the P100 latency of VEP in PD patients. The VEP results suggest that dysfunction in the central visual system plays a role in abnormal pattern VEP in PD. In conclusion, the present results show that these three dementing diseases have different electrophysiological features, which may be related to the underlying pathogenic mechanisms. Additionally, the measurement of multimodal evoked potentials may be helpful in the differential diagnosis of patients with dementia.

Aged↗

Noninvasive localization of brain-stem lesions in the cat with multimodality evoked potentials: correlation with human head-injury data.

Multimodality evoked potential (MEP) data from over 300 comatose head-injured patients suggest that central nervous system dysfunction of the brain stem and/or hemispheres can be localized with this noninvasive neuroelectric technique. Based on this work, decerebrate motor posturing and prolonged coma are not associated with brain-stem dysfunction but rather with dysfunction of the hemispheres, while absent pupillary and oculocephalic responses are correlated with brain-stem dysfunction alone. However, the accuracy with which MEP data localized human brain-stem or hemispheric dysfunction could not be confirmed by pathological correlation because of low mortality and the small number of autopsies obtained in the patients who died. Therefore, this study was undertaken in an animal model of brain-stem lesion. Complete brain-stem transections were made at the cervicomedullary junction, the medulla just caudal to the eighth nerve, and at the intercollicular region. All cortical visual evoked potential (VEP) peaks were reduced in amplitude and delayed by each of the brain stem transections, but none of the peaks was abolished. In spite of brain-stem transection, VEP's can be used to gain information about hemispheric function. Somatosensory (SEP) and auditory cortically generated evoked potentials (AEP) were abolished by these brain-stem transections, but early-latency brain-stem SEP and AEP data could accurately localize specific areas of brain-stem dysfunction caused by the lesions. Observations made on human MEP data seen to be confirmed by these animal experiments. Correlations between human and cat MEP data are discussed.

Animals↗

Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure.

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Adult↗

Prognostic implications of early multimodality evoked potentials in severely head-injured patients. A prospective study.

Results of multimodality evoked potential (MEP) studies recorded from 100 comatose patients soon after severe head injury were analyzed prospectively, using a previously established grading system, to assess the prognostic value of MEP's with respect to patient outcome, to evaluate the effect of clinically relevant sequelae of head injury on the prediction of outcome by MEP's and to describe time to clinical recovery as a function of initial MEP grade. Graded MEP's when recorded in the first few days after head injury, could predict patient outcome at 1 year with approximately 80% accuracy. Exclusion from the analysis of patients who died from causes unrelated to the brain and those with severe systemic complications that occurred after the evoked potentials were recorded improved the accuracy of outcome prediction to nearly 100%. The presence of a mass lesion requiring surgery reduces the probability if good to moderate outcome for a given MEP grade by approximately 25% to 40% from the seen in patients without mass lesions. The clinical outcome predicted shortly after head injury by MEP grades may not be realized for many months. Patients with mild MEP abnormality (Grade I or II) generally reach their outcome by 3 to 6 months, whereas those with more severe deficits (Grade III) may not show improvement for at least 1 year.

Adolescent↗

The effects of deep barbiturate coma on multimodality evoked potentials.

The authors report their investigation of the effects of high-dose barbiturates on the multimodality evoked response in 9 cats. After baseline evoked responses were obtained, boluses of pentobarbital were infused intravenously at regular intervals, amounting to cumulative total doses of 9, 18, 27, 45, 63, 123, and 183 mg/kg at respective infusions. This resulted in gradually increasing serum pentobarbital levels, reaching therapeutic coma levels (4 to 5 mg/dl) after the fifth infusion. At this point, the electroencephalogram was flat, and pressor agents were required to maintain cardiovascular stability. Evoked responses were obtained 15 minutes after each infusion. Brain-stem auditory evoked response (BAER) showed little change in wave latencies at therapeutic coma levels of pentobarbital. Further barbiturates resulted in delay of the late components of this response. In the somatosensory evoked responses (SER), early brain-stem components were relatively unaffected by therapeutic coma levels. Late brain-stem components and the initial cortical response showed progressive latency increase. Late cortical (association cortex) waves were abolished at relatively low doses. The central conduction time was relatively unaffected. The late waves of the visual evoked responses (VER) were abolished with low-dose barbiturates (9 mg/kg). A single positive-negative complex persisted despite massive infusions. It is concluded that evoked responses may prove useful in monitoring patients in deep barbiturate coma, but barbiturate effects must be kept in mind.

Animals↗

Fatal progression of posttraumatic dural arteriovenous fistulas refractory to multimodal therapy. Case report.

The authors report the case of a man who suffered from progressive, disseminated posttraumatic dural arteriovenous fistulas (DAVFs) resulting in death, despite aggressive endovascular, surgical, and radiosurgical treatment. This 31-year-old man was struck on the head while playing basketball. Two weeks later a soft, pulsatile mass developed at his vertex, and the man began to experience pulsatile tinnitus and progressive headaches. Magnetic resonance imaging and subsequent angiography revealed multiple AVFs in the scalp, calvaria, and dura, with drainage into the superior sagittal sinus. The patient was treated initially with transarterial embolization in five stages, followed by vertex craniotomy and surgical resection of the AVFs. However, multiple additional DAVFs developed over the bilateral convexities, the falx, and the tentorium. Subsequent treatment entailed 15 stages of transarterial embolization; seven stages of transvenous embolization, including complete occlusion of the sagittal sinus and partial occlusion of the straight sinus; three stages of stereotactic radiosurgery; and a second craniotomy with aggressive disconnection of the DAVFs. Unfortunately, the fistulas continued to progress, resulting in diffuse venous hypertension, multiple intracerebral hemorrhages in both hemispheres, and, ultimately, death nearly 5 years after the initial trauma. Endovascular, surgical, and radiosurgical treatments are successful in curing most patients with DAVFs. The failure of multimodal therapy and the fulminant progression and disseminated nature of this patient's disease are unique.

Adult↗

Multimodal treatment of ruptured dissecting aneurysms of the vertebral artery during the acute stage.

OBJECT: The goal of this study was to implement an algorithm for and assess the multimodal (endovascular and microsurgical) treatment of patients with ruptured dissecting aneurysms of the vertebral artery (VA) during the acute stage. METHODS: During a 4-year period, the authors treated 19 ruptured dissecting aneurysms of the VA during the acute stage, within 3 days after the hemorrhage. Factors guiding management decisions were tolerance of the test occlusion and the site of the dissection. The algorithm takes into account these factors to select among treatment options, that is, trapping of the VA with Guglielmi Detachable Coils (GDCs); trapping of the VA and revascularization of the posterior inferior cerebellar artery (PICA); trapping of the VA and VA-posterior cerebral artery (PCA) anastomosis; and trapping of the VA, VA-PCA anastomosis, and revascularization of the PICA. Of the 15 aneurysms without PICA involvement, 14 were treated by trapping of the VA with GDCs and one by trapping of the VA and a VA-PCA bypass. The other four aneurysms with PICA involvement were treated by VA trapping and PICA revascularization. There was no episode of recurrent hemorrhage or ischemia during the posttreatment follow-up period. Although lateral medullary syndrome developed as a permanent complication in one patient, a good recovery was made by the other 18 patients by 6 months after the ictus. CONCLUSIONS: The factors that determine the appropriate treatment for ruptured dissecting aneurysms of the VA are tolerance of a test occlusion and the site of dissection. Favorable patient outcomes can be achieved when this algorithm is used.

Adult↗

Multimodality intraoperative monitoring during complex lumbosacral procedures: indications, techniques, and long-term follow-up review of 61 consecutive cases.

OBJECT: The purpose of this study was to examine the neurological outcomes after complex lumbosacral surgery in patients undergoing multimodality neurophysiological monitoring. METHODS: Sixty-one patients were consecutively enrolled in this study. These patients underwent complex intra- and extradural lumbosacral procedures with concomitant intraoperative electromyography (EMG) monitoring of the lower-limb muscles, external anal and urethral sphincters (EAS and EUS), and lower-limb somatosensory evoked potentials (SSEPs). Long-term (minimum 2-year) clinical follow-up data were obtained in all cases. Most patients were treated for spinal/spinal cord tumors (61%) or adult tethered cord syndrome (25%). Recordable lower-extremity SSEPs were reported in 54 patients (89%). New postoperative neurological deficits occurred in only three patients (4.9%), and remained persistent in only one patient (1.6%) at long-term follow-up examination. In only one of these cases was a significant decrease in SSEP amplitude detected. Spontaneous EMG activity was observed in the lower-extremity muscles and/or EAS and EUS in 51 cases (84%). Intraoperatively, EMG demonstrated activity only in the EUS in 5% of patients and only in the EAS in 28%. In seven patients (11%) spontaneous intraoperative EMG activity was observed in both the EAS and the EUS; however, in only three of these cases was EMG activity recorded in both sphincters simultaneously. In addition to spontaneously recorded EMG activity, electrically evoked EMG activity was also used as an intraoperative adjunct. A bipolar stimulating electrode was used to identify functional neural tissue before undertaking microsurgical dissection in 58 individuals (95%). In the majority of these patients, evoked EMG activity occurred either in one (33%) or in two muscles (9%) simultaneously. The presence of electrically evoked EMG activity in structures encountered during microdissection altered the plan of treatment in 24 cases (42%). CONCLUSIONS: The authors conclude that the combined SSEP and EMG monitoring of lower-limb muscles, EAS, and EUS is a practical and reliable method for obtaining optimal electrophysiological feedback during complex neurosurgical procedures involving the conus medullaris and cauda equina. Analysis of the results indicates that these intraoperative adjunctive modalities positively influence decision making with regard to microsurgery and reduce the risk of perioperative neurological complications. Validation of the clinical value of these approaches, however, will require further assessment in a larger prospective cohort of patients.

Adolescent↗

Multimodality approaches for pancreatic cancer.

The role of combined-modality therapy for pancreatic cancer is evolving with the recent development and completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive chemoradiotherapy or adjuvant chemoradiotherapy for local and/or regionally advanced disease. Our aim is to summarize the current state-of-the-art management and future directions regarding the multimodality approach to pancreatic cancer.

Angiogenesis Inhibitors↗

A Knowledge-Enhanced Multimodal Framework with Genomic Reconstruction for DLBCL Drug Response Prediction.

Diffuse large B-cell lymphoma (DLBCL) exhibits substantial biological heterogeneity, leading to pronounced variability in patient response to therapy. Accurate drug response prediction is therefore critical for precision treatment but remains challenging in clinical settings where genomic sequencing, a highly informative modality, is frequently incomplete. Existing methods, often developed from cell-line pharmacogenomic datasets or single-modality data, typically assume fully observed molecular profiles and thus show limited robustness under missing genomic data. To address this limitation, a knowledge-enhanced multimodal framework with genomic reconstruction (KeM-DRP) is proposed for individualized drug response prediction in DLBCL. The framework models the central role of genomics by integrating biological prior knowledge through a gene-pathway-biological process hierarchy, enabling robust representation learning from sparse observations. To compensate for missing genomic measurements, a cross-modal genomic compensation module reconstructs genomically informed latent features from routinely available clinical modalities. Furthermore, a genomics-guided adaptive fusion strategy dynamically integrates heterogeneous modalities conditioned on observed or reconstructed genomic representation. Experiments on a real-world DLBCL cohort demonstrate that KeM-DRP consistently outperforms competitive baselines. The reconstructed genomic representation represents most predictive utility, highlighting the robustness and practical value of the framework under incomplete genomic data.

Journal Article↗

Chemotherapy as a component of multimodal therapy for gastric carcinoma.

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase III trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced (T2-stage) cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase II trials using active drug combinations. In 2005, a large phase III trial testing pre- and postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase III studies testing this strategy may be warranted in the near future.

Chemotherapy, Adjuvant↗

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein.

AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P < 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.

Adult↗

The NITE XML Toolkit: flexible annotation for multimodal language data.

Multimodal corpora that show humans interacting via language are now relatively easy to collect. Current tools allow one either to apply sets of time-stamped codes to the data and consider their timing and sequencing or to describe some specific linguistic structure that is present in the data, built over the top of some form of transcription. To further our understanding of human communication, the research community needs code sets with both timings and structure, designed flexibly to address the research questions at hand. The NITE XML Toolkit offers library support that software developers can call upon when writing tools for such code sets and, thus, enables richer analyses than have previously been possible. It includes data handling, a query language containing both structural and temporal constructs, components that can be used to build graphical interfaces, sample programs that demonstrate how to use the libraries, a tool for running queries, and an experimental engine that builds interfaces on the basis of declarative specifications.

Communication↗

Multimodality treatment of resectable non small-cell lung cancer.

In early-stage, resectable non small-cell lung cancer other than stage IA, survival following surgical resection has been disappointing. Many phase III adjuvant trials using postoperative chemotherapy, radiotherapy, or chemoradiation have had disappointing results results that have been confirmed by two recent meta-analyses. Preoperative radiotherapy combined with surgery has also failed to improve survival following surgical resection. For the past 20 years, several phase II trials have investigated the use of induction therapies (chemotherapy or chemoradiation) prior to surgery in the management of stage IIIA lung cancer. The phase II trials have been encouraging, and two small phase III trials have confirmed the efficacy of the multimodality approach. Newer, more tolerable chemotherapeutic agents are now being investigated. Because of the encouraging results in locally advanced disease, this induction therapy has been used in two trials of early stage (IB, II) disease; both trials have suggested that induction therapy improved patient tolerance to chemotherapy and in one trial perhaps improved survival. Currently, several phase III trials are attempting to confirm these early encouraging reports.

Journal Article↗

Integration of multimodality approaches in the management of malignant pleural mesothelioma.

More than half a century after the first descriptions of mesothelioma as a pathologic entity, satisfactory treatment is still elusive. Although relatively uncommon, the incidence of mesothelioma will most likely increase over the next 10-20 years. Advances have been made in understanding the pathogenesis, diagnosis, and staging, but they have not translated into markedly improved survival. Some use palliative treatment as the primary means of therapy even now. On the other hand, a cadre of individuals have studied how surgery, chemotherapy, and radiation therapy affect the disease. Although each individual modality has had limited success by itself, a multimodality approach has been documented to improve survival and quality of life. In addition, intriguing discoveries in immunology and gene profiling and therapy promise hope for further improvement. In this article, we will illustrate the current views on integrating these different approaches and delineate areas of active research.

Antineoplastic Combined Chemotherapy Protocols↗

Multimodality treatment in a case of primary cardiac lymphoma.

Primary cardiac lymphoma(PCL) is an exceptionally rare entity associated with a poor progonosis. The patient in this report underwent successful surgical resection of a PCL. We now describe her multimodality treatment including autologous stem cell transplantation which resulted in a 22 month survival.

Antineoplastic Combined Chemotherapy Protocols↗

Development and Validation of a Multimodal Clinical, Pathologic, and Genomic Model for Breast Cancer Recurrence.

PURPOSE: To develop and validate a multimodal recurrence-risk model integrating histology, genomic testing, and clinical variables. METHODS: We developed AI-Path, a whole-slide image biomarker for recurrence prediction trained in CALGB 9344, and validated it in three independent cohorts: TAILORx, a multi-site Chicago cohort, and the MDX-BRCA cohort. We then integrated AI-Path with Oncotype DX Recurrence Score (RS), tumor size, and nodal status into a Cox model, PathClinRS, fit using 60% of cases from TAILORx, with the remaining 40% held out for validation. The primary end point was distant recurrence-free interval. Performance was assessed using Harrell's concordance index (C-index) and Kaplan-Meier analyses. RESULTS: A total of 12,418 patients were included. In TAILORx, AI-Path outperformed RS for distant recurrence (C-index, 0.682 vs 0.647; P = .038), driven by superior prediction of late recurrence (0.656 vs 0.567; P < .001). In node-negative disease, PathClinRS outperformed RSClin in the TAILORx fitting (0.72 vs 0.70; P = .016) and validation sets (0.74 vs 0.70; P = .004). In node-positive disease, PathClinRS outperformed RSClinN+ in Chicago (0.94 vs 0.74; P < .001) and MDX-BRCA (0.71 vs 0.66; P = .004) cohorts. Compared with NATALEE eligibility, PathClinRS identified nearly twice as many high-risk node-negative patients while maintaining a comparable 10-year distant recurrence risk (16.7% vs 16.6% per NATALEE eligibility in TAILORx fitting; 21.0% vs 19.4% in TAILORx validation). PathClinRS identified 68% of intermediate risk premenopausal patients as low-risk with no evidence of chemotherapy benefit, compared to only 36% identified as low risk by standard clinicopathologic criteria. CONCLUSION: Digital histopathology provides prognostic information complementary to genomic assays and has the potential to personalize therapy beyond existing clinicogenomic tools.

Journal Article↗