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Improving treatment planning accuracy through multimodality imaging.

PURPOSE: In clinical practice, physicians are constantly comparing multiple images taken at various times during the patient's treatment course. One goal of such a comparison is to accurately define the gross tumor volume (GTV). The introduction of three-dimensional treatment planning has greatly enhanced the ability to define the GTV, but there are times when the GTV is not visible on the treatment-planning computed tomography (CT) scan. We have modified our treatment-planning software to allow for interactive display of multiple, registered images that enhance the physician's ability to accurately determine the GTV. METHODS AND MATERIALS: Images are registered using interactive tools developed at the University of North Carolina at Chapel Hill (UNC). Automated methods are also available. Images registered with the treatment-planning CT scan are digitized from film. After a physician has approved the registration, the registered images are made available to the treatment-planning software. Structures and volumes of interest are contoured on all images. In the beam's eye view, wire loop representations of these structures can be visualized from all image types simultaneously. Each registered image can be seamlessly viewed during the treatment-planning process, and all contours from all image types can be seen on any registered image. A beam may, therefore, be designed based on any contour. RESULTS: Nineteen patients have been planned and treated using multimodality imaging from November 1993 through August 1994. All registered images were digitized from film, and many were from outside institutions. Brain has been the most common site (12), but the techniques of registration and image display have also been used for the thorax (4), abdomen (2), and extremity (1). The registered image has been an magnetic resonance (MR) scan in 15 cases and a diagnostic CT scan in 5 cases. In one case, sequential MRs, one before treatment and another after 30 Gy, were used to plan patient's initial fields and boost, respectively. Case illustrations are shown. CONCLUSIONS: We have successfully integrated multimodality imaging into our treatment-planning system, and its routine use is increasing. Multimodality imaging holds out the promise of improving treatment planning accuracy and, thus, takes maximum advantage of three dimensional treatment planning systems.

Humans↗

Multimodal patient education program with stress management for childhood and adolescent asthma.

The present study aimed to evaluate a multimodal patient education program carried out during inpatient rehabilitation. The program included cognitive-behavioral stress management training as a main component. The efficacy was examined in comparison to an education program without stress management. In total N=68 patients aged between 8 and 16 years were included in the post-treatment and N=46 patients in the 6 months follow-up assessment. Short- and long-term intervention effects of the multimodal education program were observed in relation to patients' age. The experimental treatment elicited significant improvements in adaptive coping in adolescents aged from 14 to 16 years. In contrast, substantial effects were not yielded for the control treatment. The results suggest that the multimodal patient education training has beneficial effects on stress management in adolescents with asthma. Results are discussed with regard to predictive factors for rehabilitation outcome.

Adaptation, Psychological↗

Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy.

We report the medium-term (median follow-up=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.

Adult↗

Locally advanced breast cancer: early results of a randomised trial of multimodal therapy versus initial hormone therapy.

The aim of this study was to investigate initial treatment of locally advanced breast cancer. Patients were randomised to "multimodal" therapy (pre-operative chemotherapy, Patey mastectomy, flap irradiation and adjuvant hormone therapy) (n = 55), or initial "hormone" therapy (n = 53) with further therapy upon tumour progression. The objective response to chemotherapy was 57% (31/54) after four cycles. Of patients on hormone therapy, 36% (19/53) had an objective response and 32% (17/53) disease stasis at a 6 month assessment. At a median 30 months follow-up, there was no notable difference in development of metastases or survival: only 6 patients have uncontrolled loco-regional relapse (4 "hormonal", 2 "multimodal"). The number of treatments per patient required for this loco-regional control was lower in the "hormone" group (mean 2.13 versus 4.20 in the "multimodal" group). This small study has shown that the use of consecutive therapies, with the aim of tumour control, does not appear to compromise outcome in comparison with initial "multi-modal" therapy. Adopting such a policy may allow some patients to avoid unnecessary treatments.

Adult↗

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Abdomen↗

Urologic and sexual morbidity following multimodality treatment for locally advanced primary and locally recurrent rectal cancer.

AIMS: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer much attention is given to the oncological aspects. In long-term survivors, urogenital morbidity can have a large effect on the quality of life. This study evaluates the functional outcome after multimodality treatment in these patient groups. PATIENTS AND METHODS: Between 1994 and August 1999, 55 patients with locally advanced primary and 66 patients with locally recurrent rectal cancer were treated with multimodality treatment: i.e. high-dose preoperative external beam radiation therapy, followed by extended surgery and intraoperative radiotherapy. The medical records of the 121 patients were reviewed. To assess long-term urogenital morbidity, all patients still alive, with a minimum follow-up of 4 months, were asked to fill out a questionnaire about their voiding and sexual function. Seventy-six of the 79 currently living patients (96%) returned the questionnaire (median FU 14 months, range 4-60). RESULTS: The questionnaire revealed identifiable voiding dysfunction as a new problem in 31% of the male and 58% of the female patients. In 42% of patients after locally advanced primary and 48% after locally recurrent rectal cancer treatment bladder dysfunction occurred. The preoperative ability to have an orgasm had disappeared in 50% of the male and 50% of the female patients, and in 45% of patients after locally advanced primary and in 57% after locally recurrent rectal cancer treatment. CONCLUSION: Multimodality treatment for locally advanced primary and recurrent rectal cancer results in acceptable urogenital dysfunction if weighed by the risk of uncontrolled tumour progression. Long-term voiding and sexual function is decreased in half of the patients. Preoperative counselling of these patients on treatment-related urogenital morbidity is important.

Adult↗

Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair.

BACKGROUND AND OBJECTIVES: Administration of analgesic medication before surgery, rather than at the completion of the procedure, may reduce postoperative pain. Similarly, administration of multiple analgesics, with different mechanisms of action, may provide improved postoperative pain control and functional recovery. The purpose of our study was to compare pain scores and intravenous opioid consumption after outpatient anterior cruciate ligament (ACL) reconstruction in patients who received a multimodal drug combination (intravenous [IV] ketorolac, intra-articular morphine/ropivacaine/epinephrine, and femoral nerve block with ropivacaine) either before surgery or immediately at the completion of the surgical procedure. METHODS: Forty patients presenting for same-day arthroscopic ACL repair using a semitendinosis tendon graft were included in this study. The patients were randomized to receive the following drugs either 15 minutes before skin incision or immediately after skin closure: (1) Ketorolac 30 mg IV. (2) Intra-articular injection of 20 mL ropivacaine 0.25% + morphine 2 mg and epinephrine 1:200,000. (3) Femoral nerve block with 20 mL ropivacaine 0.25%. Verbal pain scores were obtained in the postanesthesia care unit (PACU) and on postoperative days 1, 3, and 7. IV patient controlled analgesia (PCA) morphine consumption in the PACU was also recorded. RESULTS: Verbal pain rating scores were lower in group I (preemptive) for 2.0 hours after arrival in the PACU. There was no difference between groups in pain scores on postoperative days 1, 3, and 7. Mean IV PCA morphine consumption in the PACU was lower in group I (6.4 mg) versus group II (12.3 mg), P <.05. CONCLUSION: Preemptive, multimodal administration of our 3-component analgesic drug combination resulted in lower pain scores during the initial stay in the PACU unit and lower consumption of IV PCA morphine in the PACU. However, pain scores were similar in both groups on postoperative days 1, 3, and 7; thus, there was no measurable long-term advantage associated with preemptive multimodal drug administration.

Adult↗

[Radicular Low Back Pain: Evaluation of Conservative Multimodal Treatment]

OBJECTIVE: In this summary, the preliminary results of studies evaluating medical therapy of radicular low back pain are reported. METHODS: In two prospective cohorts (183 patients) the conservative multimodal inpatient treatment was examined, using the newly developed "Radicular Low Back Pain Score" for the standardized measurement of the radiculopathy. In another sample of 116 patients the preceeding outpatient treatment was documented. RESULTS: A significant short-term improvement with regard to the pain intensity and the radiculopathy was observed after approximately two weeks of therapy. The preceeding outpatient treatment did not comply with recent guidelines. Moreover, it did not influence the outcome of the multimodal inpatient therapy. CONCLUSIONS: The "Radicular Low Back Pain Score" seems to be a suitable instrument for measuring therapy effectiveness. Multimodal medical treatment is an important treatment approach for sciatica, especially after failed outpatient therapy.

Journal Article↗

Stroop interference based on the multimodal correlates of haptic size and auditory pitch.

In a preliminary experiment subjects were asked to explore three wooden knobs of different sizes and to rate each one on a series of 7-point scales. The results confirmed that an object may possess a number of multimodal qualities that are contingent on its haptic size. The pattern of intercorrelations between the qualities was consistent with the pattern that is observed when subjects respond to pure auditory tones varying in pitch. For example, small (high-pitched) sounds, like small objects, are judged to be sharp, thin, light, weak, fast, tense, and bright. The main experiments used a paradigm based on the Stroop interference effect. Subjects were required to press one of two keys as quickly as possible depending on which of four possible words appeared in the centre of the screen. A 50 Hz or a 5500 Hz tone accompanied each test word, and subjects responded on two keys that differed in size. Subjects were found to respond more slowly when either the pitch of the incidental sound or the size of the key on which they responded was incongruent with the multimodal features represented by the test word. The results confirm that people are automatically and immediately sensitive to the multimodal features of a stimulus when direct sensory evidence for the features is absent.

Form Perception↗

Multimodal feedback: an assessment of performance and mental workload.

Multimodal interfaces offer great potential to humanize interactions with computers by employing a multitude of perceptual channels. This paper reports on a novel multimodal interface using auditory, haptic and visual feedback in a direct manipulation task to establish new recommendations for multimodal feedback, in particular uni-, bi- and trimodal feedback. A close examination of combinations of uni-, bi- and trimodal feedback is necessary to determine which enhances performance without increasing workload. Thirty-two participants were asked to complete a task consisting of a series of 'drag-and-drops' while the type of feedback was manipulated. Each participant was exposed to three unimodal feedback conditions, three bimodal feedback conditions and one trimodal feedback condition that used auditory, visual and haptic feedback alone, and in combination. Performance under the different conditions was assessed with measures of trial completion time, target highlight time and a self-reported workload assessment captured by the NASA Task Load Index (NASA-TLX). The findings suggest that certain types of bimodal feedback can enhance performance while lowering self-perceived mental demand.

Adult↗

mmContext: an open framework for multimodal contrastive learning of omics and text data.

SUMMARY: Multimodal approaches are increasingly leveraged for integrating omics data with textual biological knowledge. Yet there is still no accessible, standardized framework that enables systematic comparison of omics representations with different text encoders within a unified workflow. We present mmContext, a lightweight and extensible multimodal embedding framework built on top of the open-source Sentence Transformers library. The software allows researchers to train or apply models that jointly embed omics and text data using any numeric representation stored in an AnnData.obsm layer and any text encoder available in Hugging Face. mmContext supports integration of diverse biological text sources and provides pipelines for training, evaluation, and data preparation. We train and evaluate models for a RNA-Seq and text integration task, and demonstrate their utility through zero-shot classification of cell types and diseases across four independent datasets. By releasing all models, datasets, and tutorials openly, mmContext enables reproducible and accessible multimodal learning for omics-text integration. AVAILABILITY AND IMPLEMENTATION: Pretrained checkpoints and full source code for our custom MMContextEncoder are available on Hugging Face huggingface.co/jo-mengr. The Python package github.com/mengerj/mmcontext provides the model implementation and training and evaluation scripts for custom training. The releases for the publication can be accessed via zenodo: adata_hf_datasets: doi.org/10.5281/zenodo.19185217 and mmContext: doi.org/10.5281/zenodo.19185493.

Computational Biology↗

Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters.

OBJECTIVE: To determine the long-term results of liver transplantation for hepatocellular carcinoma (HCC) measuring 5 cm or larger treated in a multimodality adjuvant protocol. SUMMARY BACKGROUND DATA: Transplant has been established as a viable treatment of HCC measuring less than 5 cm, but the results for larger tumors have been disappointing. Several studies have shown promising preliminary results when combining transplant with preoperative transarterial chemoembolization and/or perioperative systemic chemotherapy in the treatment of advanced HCC that is not amenable to resection. However, follow-up in the studies has been limited and the number of patients has been small. METHODS: Beginning in October 1991, all patients with unresectable HCC measuring 5 cm or larger, as measured by computed tomography, were considered for enrollment in the authors' multimodality protocol. Entry criteria required that all patients be free of extrahepatic disease based on computed tomography scans of the chest and abdomen and bone scan and have a patent main portal vein and major hepatic veins on duplex ultrasonography. Patients received subselective arterial chemoembolization with mitomycin C, doxorubicin, and cisplatin at the time of diagnosis, repeated as necessary based on tumor response. Patients received a single systemic intraoperative dose of doxorubicin (10 mg/m(2)) before revascularization of the new liver and systemic doxorubicin (50 mg/m(2)) every 3 weeks as tolerated, for a total of six cycles, beginning on the sixth postoperative week. RESULTS: Eighty patients were enrolled; 37 were eventually excluded, due mainly to disease progression while on the waiting list, and 43 underwent liver transplant. Mean pathologic tumor diameter was 5.8 +/- 2.7 cm. Median follow-up of surviving transplanted patients was 55.1 +/- 24.9 months. There were two (4.7%) perioperative deaths. Median overall survival was significantly longer in transplanted patients (49.9 +/- 10.42 months) than in those who were excluded (6.83 +/- 1.34 months). Overall and recurrence-free survival rates in transplanted patients at 5 years were 44% and 48%, respectively. A tumor size larger than 7 cm and the presence of vascular invasion correlated significantly with recurrence. Recurrence-free survival at 5 years was significantly higher for the 32 patients with tumors measuring 5 to 7 cm (55%) than the 12 patients with tumors larger than 7 cm (34%). CONCLUSIONS: A significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy. Patients with tumors measuring 5 to 7 cm have significantly longer recurrence-free survival compared with those with larger tumors.

Aged↗

Multimodality imaging for precise localization of craniofacial osteomyelitis.

Functional imaging identifies areas of abnormal bone turnover, providing a useful adjunct in the treatment of osteomyelitis and bone tumors. The low resolution and lack of anatomical detail limit the application of bone scans in craniofacial surgery, however. Multimodality image registration addresses this problem by fusing functional images (single photon emission computed tomography [SPECT]) to high-resolution structural images (computed tomography [CT]) for precise anatomical delineation of bone activity. This article describes a technique for spatial registration of CT and SPECT images to provide precise anatomical delineation of abnormal bone turnover, thereby guiding the extent of resection in the management of craniofacial osteomyelitis. Standard CT and SPECT imaging protocols were used in imaging the skull from the vertex to the mentum. Image data were imported into Analyze (Biomedical Imaging Resource; Mayo Foundation, Rochester, MN) on a dedicated Windows NT (Microsoft Corporation, Redmond, WA) workstation. Using the CT data, the craniofacial skeleton, osteotomy segments, and bone grafts were interactively mapped out. Consecutive axial slices were then reconstructed to form a three-dimensional volume of interest. The CT-derived volume of interest was registered to the technetium Tc 99m-methylene diphosphonate SPECT scan using the Analyze program to provide a fused multimodality image. The imaging technique was used to localize osteomyelitis in a complex craniofacial reconstruction. The fused images guided the extent of resection during surgery, and postoperative microbiological and histological testing confirmed the diagnosis. Multimodality image registration provides a readily available method to relate facial skeletal anatomy and physiology. This technique is valuable in planning and monitoring therapeutic interventions in clinical conditions in which bone turnover is abnormal.

Adult↗

Multimodal medullary neurons and correlational linkages of the respiratory network.

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan-anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and "limit" changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.

Animals↗

Selective spatial attention in vision and touch: unimodal and multimodal mechanisms revealed by PET.

Two positron-emission tomography (PET) experiments explored the neural basis of selective spatial attention in vision and touch, testing for modality-specific versus multimodal activations due to attended side. In the first study, either light flashes or finger vibrations were presented bilaterally. Twelve healthy volunteers were scanned while sustaining covert attention on the left or right hemifield within each modality. The main effect for attending right minus left, across both modalities, revealed bimodal spatial attention effects in the left intraparietal sulcus and left occipitotemporal junction. Modality-specific attentional effects (again, for attending right vs. left) were found in the left superior occipital gyrus for vision, and left superior postcentral gyrus for touch. No significant activations were seen for attending left minus right. The second study presented only tactile stimuli, manipulating whether the eyes were open or closed, and including passive stimulation and rest baselines. The unimodal activation for tactile spatial attention in the left superior postcentral gyrus was replicated. The bimodal activation of the left intraparietal sulcus observed in the first study was now found for touch, but only when the eyes were open (hands visible), apparently confirming its multimodal nature. These results reveal mechanisms of sustained spatial attention operating at both modality-specific and multimodal levels.

Adult↗

Multisensory cues and multimodal communication in spiders: insights from video/audio playback studies.

Spiders perceive the world using multiple sensory modes, including vibration, vision, and chemical senses, for prey detection and communication. These sensory modes are used in many communication contexts, either individually or in multimodal signaling. Selection for effective signaler-receiver communication and species discrimination is especially strong for these predatory and potentially cannibalistic arthropods, resulting in the evolution of considerable diversity in signaling behaviors. In this paper, we review sensory mechanisms involved in spider signaling and present an overview of recent work done on wolf spiders (Lycosidae) that use multimodal communication (simultaneous visual and vibratory signals) in sexual signals during courtship. The relative importance of visual and vibratory signaling modes, and the use of multiple modes varies among closely related species in the genus Schizocosa, providing a model system for investigating multisensory guidance of complex behavior. Here we examine previous and current research on responses of female spiders to components of male courtship behavior, using several experimental techniques including cue isolation (single sensory modes), video/audio digitization and playback, and cue-conflict (mixed conspecific/heterospecific components) to tease apart elements of multimodal signaling.

Animal Communication↗

Multimodal online monitoring in middle cerebral artery territory stroke.

BACKGROUND AND PURPOSE: Patients with large middle cerebral artery infarction and elevated intracranial pressure (ICP) who are undergoing invasive intensive care therapy require technical monitoring. However, the effectiveness of the current gold standard, measurement of ICP, is limited. Furthermore, the effects of what is considered to be standard antiedema medical treatment are not fully understood. We studied whether multimodal monitoring can help to overcome this problem. METHODS: ICP, cerebral perfusion pressure (CPP), and partial brain tissue oxygen pressure (PbrO(2)) were continuously measured within the white matter of the frontal lobe unilaterally or bilaterally. We analyzed the effects of antiedema drugs and looked for pattern changes in the PbrO(2) before transtentorial herniation in patients in whom this could not be prevented. Furthermore, complications were registered. RESULTS: We performed 27 measurements in 21 patients. A total of 297 antiedema drug administrations were analyzed in 11 patients. Hyper-HAES and mannitol were most often associated with an increase in CPP and PbrO(2), whereas the use of thiopental and tromethamine led to negative or contrary effects, although ICP was decreased in every case. Pattern changes in the PbrO(2) curve could be observed between 6 to 18 hours before transtentorial herniation. No bleeding complication or infections were observed. CONCLUSIONS: Multimodal monitoring can be used to monitor antiedema drug effects. Our data suggest that with multimodal monitoring, pathophysiological changes could be predicted considerably in advance. ICP alone is of questionable use. Furthermore, this method might help to optimize the timing of invasive therapy in space-occupying infarction.

Brain Edema↗

Aims and methodological problems in multimodal treatment studies.

The paper outlines the growing acceptance and use of multimodal treatment approaches to treat a variety of psychiatric disorders in childhood and adolescence. It then explores some of the problems of multimodal treatment studies. Problems in assessing outcome of efficacy of the interventions, particularly as they pertain to specific interventions and particular areas of functioning are discussed as well as the issues of appropriate control and comparison groups. The problems with regard to appropriate control and comparison groups are explored with respect to diagnosis and interventions. Finally, an ongoing multimodal treatment study of children with attention deficit hyperactive disorder is used to illustrate how some of the problems described can be solved.

Adolescent↗