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Advanced multimodal visualisation of clinical gait and fluoroscopy analyses in the assessment of total knee replacement.

Traditional gait and fluoroscopy analysis of human movement are largely utilised but are still limited in registration, integration, synchronisation and visualisation capabilities. The present work exploits the features of a recently developed software tool based on multimodal display (Data Manager developed within the EU-funded project 'Multimod') in an exemplary clinical case. Standard lower limb gait analysis, comprising segment position, ground reaction force and EMG data collection, and three-dimensional fluoroscopy analysis at the replaced joint were performed in a total knee replacement patient while ascending stairs. Clinical information such as X-rays and standard scores were also available. Data Manager was able to import all this variety of data and to structure these in an original hierarchical tree. Bone and prosthesis component models were registered to corresponding marker position data for effective three-dimensional animations. These were also synchronised with corresponding standard video sequences. Animations, video, time-histories of collected and also processed data were shown in various combinations, according to specific interests of the bioengineering and medical professionals expected to observe and to interpret this large amount of data. This software tool demonstrated to be a valuable means to enhance representation and interpretation of measurements coming from human motion analysis. In a single software, a thorough and effective clinical and biomechanical analysis of human motion was performed.

Arthroplasty, Replacement, Knee↗

Robust automatic coregistration, segmentation, and classification of cell nuclei in multimodal cytopathological microscopic images.

The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on repeated staining of a cell smear. The correlation of features and data extracted from the different stains, and related to relocated individual cells, may yield a dramatic increase of diagnostic reliability. In order to utilise the technique, fully automatic, adaptive image preprocessing techniques need to be applied, which are described in this article: coregistration of multimodal images, segmentation, and classification of cell nuclei. The presented feasibility study shows both efficiency and robustness of all steps being high regarding medical image material, and it strongly supports clinical application.

Cell Nucleus↗

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology↗

Fetal magnetoencephalography--a multimodal approach.

Past studies have shown the feasibility of recording fetal evoked responses to external stimuli using a non-invasive technique called magnetoencephalography (MEG). These studies were all performed using either auditory or visual stimuli and showed a fairly low detection rate for each modality, thus making this technology currently unreliable for fetal clinical applications. This study is based on the hypothesis that a multimodal approach of applying both auditory and visual stimulation paradigms in successive recording sessions could improve the probability of obtaining a fetal evoked response. A total of 34 studies were performed on 11 normal healthy fetuses at different stages of gestation starting as early as 28 weeks with a 151-channel fetal MEG system. The success rate of obtaining a response to either (or both) stimuli from a study at a given gestation age was 91%. All the 11 fetuses showed a response at least once over the gestation period the recordings were performed. A multimodal testing approach can improve the ability of the MEG technique to reliably monitor the functional development of the fetal brain.

Acoustic Stimulation↗

Outcome after the introduction of a multimodality treatment program for locally advanced rectal cancer.

AIM: This prospective study reports the results of a multimodality treatment protocol in patients with locally advanced rectal cancer and assesses outcome after curative vs non-curative surgery and in relation to primary advanced vs locally recurrent cancer. METHODS: Between 1991 and 2002, 122 patients completed the protocol. Fifty-eight had primary advanced and sixty-four had locally recurrent rectal cancer. Median follow up was 82 months (5-143). RESULTS: A potentially curative resection was achieved in 59% of the patients with primary advanced and in 34% of patients with locally recurrent cancer. After curative resection, 53 and 59%, respectively, were free from recurrence during the observation time (median 82 months) and the overall 5-year survival was 34 and 40%. Overall 5-year survival in all patients with primary advanced cancer was 29 and 16% in all patients with locally recurrent rectal cancer. CONCLUSION: Multimodality treatment may cure at least a third of patients with locally advanced rectal cancer provided a radical resection is performed. As the post-operative morbidity is high, an optimised patient selection for neo-adjuvant treatment and surgery is essential. However, palliative surgery may benefit the patient if local control is achieved. Future studies should focus on the problem of distant metastasis.

Adult↗

Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy.

OBJECTIVES: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI). BACKGROUND: Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood. METHODS: We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone. RESULTS: Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05). CONCLUSIONS: With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.

Animals↗

Multimodal image registration for localization of sentinel nodes in head and neck squamous cell carcinoma.

PURPOSE: The aim of this clinical study was to propose a new method of preoperative 3-dimensional localization of the neck sentinel node in clinically and radiographically N0 squamous cell carcinoma of the oral cavity. PATIENTS AND METHODS: This prospective study was carried out between August 2002 and August 2003. Ten patients with staged oral squamous cell cancer underwent this method of preoperative localization of the sentinel lymph node. At the present time, lymphoscintigraphy is recognized as the investigation of choice for the preoperative detection of sentinel nodes. Although we found it to be highly sensitive (100% in our study), it does not allow precise localization of the sentinel node in the anatomic context of the neck. To overcome this drawback, we used multimodal image registration applied to the cervical region in association with the imaging modalities of scintigraphy (single-photon emission computed tomography [SPECT] and gamma transmission) and computed tomography (CT). SPECT and gamma transmission (barium-133 sources) were carried out with a triple-head Philips-Marconi camera (Philips Medical System, Cleveland, OH), and CT was carried out with a General Electric console (GE Medical Systems, Milwaukee, WI). Gamma transmission was used to place the SPECT images in a reference cervical anatomic context (CT images). Registration involved the use of a manual method based on definition of homologous volume structures. RESULTS: Preoperative image registration effectively localized the cervical sentinel node in 9 of the 10 patients, enabling a guided surgical approach in 90% of cases. The sentinel node was localized and resected using a hand-held gamma probe. CONCLUSIONS: This original study adapts a new tool (multimodal image registration) to obtain precise preoperative localization of the cervical sentinel node in N0 oral squamous cell carcinoma. We confirmed the feasibility of this method in this indication. Although this method is a novel one, we believe that it will become extremely useful once a consensus has been reached on exclusive excision of the cervical sentinel node in oral cancers, as is the case for melanoma or breast cancer.

Adult↗

Evaluation of the performance of commercially available polysaccharide-based chiral stationary phases after multicycle operation in multimodal elution mode.

The performance of four commercially available polysaccharide-based chiral stationary phases, Chiralcel OD, Chiralcel OJ, Chiralpak AD and Chiralpak AS was evaluated after several cycles of extended multimodal operations. Acetonitrile, methanol, ethanol and their mixtures were chosen for polar-organic mobile phases, ethanol-n-heptane mixture and n-heptane were selected for normal-phase mode. Retention factor (k), selectivity (alpha), resolution (Rs) and theoretical plate count (N) were the chosen parameters to describe the column performance. One racemate for which all four columns have shown enantioselectivity was chosen as test compound. After 15 cycles of multimodal operations a slight decrease was seen in the retention factors (k) however, column efficiency, selectivity (alpha) and resolution (Rs) were maintained.

Acetonitriles↗

Results of multimodal treatment for desmoplastic small round cell tumors.

PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are rare aggressive neoplasms that frequently present with large symptomatic intraabdominal masses. We examined the effects of multimodal therapy including induction chemotherapy, aggressive surgical debulking, and external beam radiotherapy on patients with DSRCT. METHODS: Institutional Review Board permission was obtained. Sixty-six patients were diagnosed by histology, immunohistochemistry, and or cytogenetics as having DSRCT at our institution from July 1, 1972, to July 1, 2003. Data were collected on patient demographics, presenting symptoms, tumor location and extent, treatment regimen, and overall survival. RESULTS: A majority of patients were male (91%), Caucasian (85%), and with a median age of 19 (7-58) years old at diagnosis. The most common presenting complaint was an intraabdominal mass (64%). In 63 patients (96%), the primary tumor was located in the abdomen or pelvis. Thirty-three (50%) had positive lymph nodes and 27 (41%) had distant parenchymal metastases at diagnosis. Overall, 3- and 5-year survivals were 44% and 15%, respectively. Twenty-nine of these patients (44%) underwent induction chemotherapy (P6), surgical debulking, and radiotherapy. Three-year survival was 55% in those receiving chemotherapy, surgery, and radiotherapy vs 27% when all 3 modalities were not used (P < .02). Gross tumor resection was highly significant in prolonging overall survival; 3-year survival was 58% in patients treated with gross tumor resection compared to no survivors past 3 years in the nonresection cohort (P < .00001). Ten patients (15%) have no evidence of disease with a median follow-up of 2.4 years (range, 0.4-11.2 years). CONCLUSIONS: Multimodal therapy results in improved survival in patients with DSRCT. Aggressive surgical resection of these extensive intraabdominal neoplasms correlates with improved patient outcome.

Abdominal Neoplasms↗

Automated CEAP Classification of Venous Duplex Reports Using Multimodal Artificial Intelligence.

OBJECTIVE: To develop and internally validate a prototype multimodal artificial intelligence system for automated CEAP (Clinical, Etiological, Anatomical and Pathophysiological) classification of venous duplex ultrasound (VDUS) reports, integrating natural language processing of free-text components with computer vision analysis of hand-drawn anatomical diagrams. METHODS: Single centre retrospective observational study using routinely collected clinical data. One thousand consecutive venous duplex ultrasound reports from Cambridge University Hospitals NHS Foundation Trust, UK (July 2024 - May 2025) were labelled according to the CEAP classification, excluding the Etiological component, which could not be reliably determined from duplex reports alone. Transfer learning was applied using ClinicalBERT for text and MobileNetV3 for diagrammatic data. Clinical classes were predicted from request line text. Text- and image-based pathophysiological models were developed for four anatomical territories (Great Saphenous Vein, Small Saphenous Vein, Deep system, Perforators), combined using late fusion with probability averaging. RESULTS: The clinical CEAP model achieved accuracy of 0.91, macro-F1 of 0.82, and macro-AUC of 0.98. Pathophysiological prediction varied, with text models broadly outperforming image models. Fusion yielded heterogeneous benefits, improving SSV performance but reducing Deep system accuracy. The performance of the final pathophysiological CEAP fusion models varied across anatomical territories: accuracy ranged from 0.70-0.92 and macro-AUC from 0.80-0.92. CONCLUSION: This study demonstrates the feasibility of automated CEAP classification from VDUS reports. Despite class imbalance affecting minority class predictions, the strong discriminatory performance validates this multimodal ML model for extracting clinically meaningful information from real-world data. This approach offers potential, pending external validation, to streamline vascular services through automated triage and guideline-compliant decision making.

Artificial intelligence↗

Multimodal management of stages III-IVa malignant thymoma.

PURPOSE: The optimal therapy for locally advanced malignant thymoma is controversial. We review our experience with a multimodal approach in 63 consecutive cases. PATIENTS AND METHODS: Forty-three patients had stage III and 20 stage IVa disease. Surgery with radical intent was initially performed in 30 cases, while 33 cases not amenable to radical surgery underwent neoadjuvant treatment (radiotherapy in 8 and chemotherapy in 25) before surgical reassessment. All patients, whether or not surgically resected, received radiation therapy. RESULTS: Radical resection (RR) was performed in 20 patients ab initio (all stage III) and in 12 patients after neoadjuvant treatment (eight stage III and four stage IVa). With the addition of patients radically operated with neoadjuvant treatment, the radical resection rate increased from 46 to 65% in stage III patients, and from 0 to 20% in those with stage IVa disease, respectively. Radical surgery was associated with longer progression free survival and overall survival according to both univariate analysis ( P< 0.001 and P<0.01, respectively) and multivariate analysis after adjustment for age, gender, histology and disease stage ( P<0.001 and <0.02, respectively). Progression free survival (median 56.9 months) was slightly lower in patients undergoing radical surgery after neoadjuvant approaches than in those radically resected ab initio (median not achieved), but overall survival (median not achieved) was similar in both groups. Subtotal surgical resection promoted complete response to subsequent radiation therapy. This condition significantly correlated with a better outcome. CONCLUSIONS: Complete surgical resection is an independent prognostic parameter in locally advanced thymoma treated with a multimodal approach. Preoperative treatment to increase the complete resection rate could improve the overall survival of these patients.

Adolescent↗

Non-small-cell lung cancer: multimodality approach in stage-III resectable disease.

The long-term results of surgery +/- radiotherapy in patients with operable disease of locally advanced non-small-cell lung cancer are discouraging. In the vast majority, disseminated microscopic disease, resulting in the later occurrence of distant metastases, contributes substantially to this poor long-term outcome. The further development of multimodality treatment approaches in randomised trials, including effective systemic therapy, is necessary. These approaches and the current status of multimodality treatment strategies of resectable locally advanced non-small-cell lung cancer are discussed.

Carcinoma, Non-Small-Cell Lung↗

Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene.

PURPOSE: Previous work showed quantitative imaging of T-cell migration into a tumor site by positron emission tomography (PET), using retroviral transduction of mutated thymidine kinase (sr39TK) reporter genes into immunized T-lymphocytes. PROCEDURES AND RESULTS: In order to improve the sensitivity and flexibility of the imaging analysis, lentivirus, that expressed sr39TK, was used to transduce the lymphocytes that migrated to an immunogenic sarcoma site. In comparison to retrovirally transduced lymphocytes, the lentivirally transduced lymphocytes showed enhanced PET signal when equal numbers of transduced lymphocytes were transferred. Furthermore, in order to utilize multimodality in vivo imaging capability, a tri-fusion reporter gene containing sr39TK, synthetic Renilla luciferase (hRluc), and enhanced green fluorescent protein (eGFP) was inserted into a lentiviral transfer vector. Using the adoptive transfer model, tumor-specific lymphocytic migration was detected by both microPET scan and bioluminescence imaging. CONCLUSION: The multimodal imaging strategy coupled with lentiviral reporter construct delivery demonstrated here can facilitate future molecular imaging studies.

Animals↗

Distinct unimodal and multimodal regions for word processing in the left temporal cortex.

How are word recognition circuits organized in the left temporal lobe? We used functional magnetic resonance imaging (fMRI) to dissect cortical word-processing circuits using three diagnostic criteria: the capacity of an area (1) to respond to words in a single modality (visual or auditory) or in both modalities, (2) to modulate its response in a top-down manner as a function of the graphemic or phonemic emphasis of the task, and (3) to show repetition suppression in response to the conscious repetition of the target word within the same sensory modality or across different modalities. The results clarify the organization of visual and auditory word-processing streams. In particular, the visual word form area (VWFA) in the left occipitotemporal sulcus appears strictly as a visual unimodal area. It is, however, bordered by a second lateral inferotemporal area which is multimodal [lateral inferotemporal multimodal area (LIMA)]. Both areas might have been confounded in past work. Our results also suggest a possible homolog of the VWFA in the auditory stream, the auditory word form area, located in the left anterior superior temporal sulcus.

Adult↗

Conservation of eyes with choroidal melanoma by a multimodality approach to treatment: an audit of 1632 patients.

OBJECTIVE: To report on conservation of eyes with choroidal melanoma with a multimodality approach to treatment. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: All 1632 patients with choroidal melanoma treated at a single center between 1993 and 2002. INTERVENTION: Primary enucleation (35%), brachytherapy (31.3%), proton beam radiotherapy (16.7%), transscleral local resection (11.0%), endoresection (3.7%), transpupillary thermotherapy (2.5%), and photocoagulation (0.1%). MAIN OUTCOME MEASURES: Primary and secondary enucleation. RESULTS: Logistic regression showed the main predictive factors for primary enucleation to be: age more than 60 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.8%-3.2%); reduced visual acuity (OR, 2.5; 95% CI, 1.9%-3.2%); posterior extension close to or involving the optic disc and fovea (OR, 1.7; 95% CI, 1.2%-2.4%); circumferential spread around the ciliary body, iris, or angle (OR, 3.1; 95% CI, 1.8%-5.5%); basal tumor diameter (OR, 3.5; 95% CI, 2.4%-5.0%); and tumor height (OR, 6.3; 95% CI, 4.5%-8.9%). After conservative treatment, the actuarial rate of secondary enucleation was 11.1% at 5 years (95% CI, 8.6%-13.6%). Cox multivariate analysis indicated the factors independently predicting secondary enucleation as: nasal/midline tumor location (risk ratio [RR], 2.6; 95% CI, 1.6%-4.4%); disc involvement (RR, 2.2; 95% CI, 1.2%-4.1%); tumor diameter (RR, 1.2; 95% CI, 1.0%-1.5%); and tumor thickness (RR, 1.8; 95% CI, 1.5%-2.1%). CONCLUSIONS: With a multimodality approach to treatment, 65% of patients underwent conservative treatment, and of them, 89% retained their eye at 5 years, with success depending on tumor diameter, tumor thickness, disc involvement, and coronal location.

Adolescent↗

Outcome of multimodal treatment for oropharyngeal carcinoma: a single institution experience.

The clinical management of patients with primary oropharyngeal squamous cell carcinoma remains controversial. The results of a combined approach involving surgery for the primary tumor, neck dissection, and postoperative radiotherapy were reviewed. A retrospective review was carried out for 211 patients meeting the inclusion criteria of resectable squamous cell carcinoma of the oropharynx. Overall survival and disease-free survival rates were calculated using the Kaplan-Meier method. Univariate (Log-rank test) and multivariate (Cox proportional hazards models) statistical analyses were carried out to investigate the role of clinical factors as significant prognostic markers. The 2- and 5-year disease-free survival rates were 79.8% and 68.8%, respectively. In univariate and multivariate analyses, positive resection margins were the only and independent significant prognostic markers for impaired disease-free survival (Log-rank: p=0.0238; Cox model: p=0.045; hazard ratio 2.48 [95% confidence interval 1.02-6.05]). In univariate analysis, male sex was the only significant negative prognostic factor for overall survival (Log-rank: p=0.0453), whereas Cox multivariate analysis identified extracapsular spread as an independent prognostics marker (p=0.049; hazard ratio 1.86 [95% confidence interval 1.00-3.43]). We conclude that the presented multimodal approach of surgery for the primary tumor and the neck followed by postoperative radio(chemo)therapy seems to be superior to non-surgical treatment protocols, as it results in better disease-free and overall survival. To assess this multimodal treatment approach, morbidity and economic considerations need to be further analyzed.

Adult↗

An experimental study of viscero-visceral hyperalgesia using an ultrasound-based multimodal sensory testing approach.

Widespread visceral hypersensitivity and the overlap of symptom complexes observed in functional gastrointestinal disorders may be related to central sensitization and neuroplastic changes. A multimodal and multi-segmental model was developed to evaluate viscero-visceral hyperalgesia induced by experimental esophageal sensitization in healthy volunteers. Twelve healthy subjects were studied using a double-blinded, placebo-controlled design. The sensitivity to mechanical and heat stimulations was assessed in the proximal esophagus, duodenum and rectum before and after perfusion of the distal esophagus with acid or saline. A special-designed probe was used allowing cross-sectional ultrasound imaging during mechanical and heat stimulation of the esophagus and duodenum. Another probe was used for mechanical stimulation of the rectum. The referred somatic pain areas to gut pain stimulations were also assessed. Following acid perfusion 11 of 12 volunteers showed increased sensitivity to one or more stimulation modalities. An overall increased sensitivity to mechanical stretch in the three gut segments was seen (P=0.0001). Posthoc analysis showed that this was mainly due to increased sensitivity in the rectum (P<0.001). No changes were seen to thermal stimulations (all P-values>0.4). The somatic referred pain area to duodenal stimulations increased (P=0.04), while it was unaffected to esophageal and rectal stimulations (P>0.3). The present method demonstrated a new approach to assess multimodal sensitivity to experimental sensitization of the esophagus and related viscero-visceral hyperalgesia. Central mechanisms can explain the remote hyperalgesia to mechanical visceral stimulation and the increase in referred pain areas. The present method may be used to explore pathophysiology and pharmacological interventions in patients with visceral hypersensitivity.

Abdominal Pain↗

Utility of multimodal evoked potentials study in neurofibromatosis type 1 of childhood.

A group of 21 children affected by neurofibromatosis type 1 has been investigated with the aim of studying multimodal (visual, brainstem auditory, and somatosensory) evoked potentials and their correlations with neurologic, electroencephalographic, and cranial magnetic resonance imaging. In the present series, cranial magnetic resonance imaging and evoked potentials were the most frequently abnormal instrumental tests. In approximately two thirds of the cases at least one of the evoked potentials (particularly visual and auditory evoked potentials) was compromised, always without clinical signs of related sensory (visual, auditory, and somatosensory) pathway pathology and sometimes in the absence of magnetic resonance imaging signs of central nervous system involvement. This study indicates that in patients with neurofibromatosis type 1, multimodal evoked potentials are useful and should be part of the diagnostic protocol of encephalic lesions together with magnetic resonance imaging. The use of both methods could aid in early detection of central nervous system dysfunction in both the initial evaluation of disease and its follow-up.

Adolescent↗