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Results for “Multimodal Fusion”

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PubMed2000

In vitro efficacy of recombinant diphtheria toxin-murine interleukin-4 immunoconjugate on mouse glioblastoma and neuroblastoma cell lines and the additive effect of radiation.

OBJECT: The prognosis for patients with primary malignant brain tumors is poor despite aggressive treatment, and tumor recurrence is common regardless of the chosen therapy. Although multimodal treatment does not provide a cure, it is necessary to determine which treatment modalities have the greatest cytotoxic effect and can potentially prolong survival. Immunotoxin therapy is a novel approach for the treatment of tumors, and it has been successfully used in the central nervous system. Because the interleukin (IL)-4 receptor is commonly expressed on brain tumor cells, the purpose of this study was to evaluate the cytotoxic effect of using a modified diphtheria toxin-murine IL-4 (DT390- mIL4) immunoconjugate for the treatment of murine brain tumor cell lines and to determine whether the addition of radiation therapy could potentiate the effect of this agent. METHODS: Spontaneous murine glioblastoma (SMA-560) and two neuroblastoma (Neuro-2a and NB41A3) cell lines were treated using DT390-mIL4 at different concentrations, and the anti-mouse IL-4 monoclonal antibody (11B11) was used for blocking its cytotoxicity. Other SMA-560 and Neuro-2a cell lines were treated using 500 cGy of radiation 3 hours before DT390-mIL4 treatment. Cytotoxity was evaluated using a trypan blue viability assay. The immunoconjugate exhibited a dose-dependent cytotoxic effect with 50% inhibitory concentration values of 0.56 x 10(-9) M in SMA-560, 1.28 x 10(-9) M in Neuro-2a, and 0.95 x (-10) M in NB41A3 cell lines. The cytotoxicity of DT390-mIL4 was specifically blocked by an excess of 11B11. Cytotoxicity was additive when the DT390-mIL4 at 10(-9) M immunoconjugate administration was followed by radiation therapy. CONCLUSIONS: These results indicate that the IL-4 receptor can be a target for diphtheria toxin fusion proteins and that radiation can potentiate the effects of DT390-mIL4. The development of multimodal approaches to treat malignant brain tumors with agents that have different mechanisms of action may be beneficial.

Animals↗

PubMed2006

Multimodal imaging of esophagus and cardia cancer before and after treatment.

PURPOSE: Prognosis and treatment of esophagus and cardia cancer (ECC) depend on the precision with which the disease is staged according to the American Joint Committee of Cancer (AJCC) criteria. Imaging modalities normally used in clinical staging are esophagography, esophagoscopy, endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography- CT fusion (CT-PET). The combination of these methods is crucial in determining not only the right diagnosis but also the stage and follow-up after multimodal treatment. The purpose of our investigation was to define the role of each imaging modality in determining the most appropriate treatment options in patients with ECC. MATERIALS AND METHODS: Fifty-six patients with ECC diagnosed by X-ray of the upper digestive tract, endoscopy and biopsy were staged using EUS, chest and abdomen CT scan, and CT-PET. Thirty-four patients in stage II and 18 patients in stage III underwent surgery after neoadjuvant chemotherapy; four patients in stage IV were treated with the positioning of an endoprosthesis after chemoradiotherapy. In the 52 patients who had surgery, follow-up included digestive tract X-ray, endoscopy and CT of the chest and abdomen every 6-8 months for the first 3 years. CT-PET was only performed in patients with a clinical suspicion of recurrence and/or CT findings suspicious of persistent disease (12 cases). RESULTS: In all 56 patients, endoscopy, EUS, CT and CT-PET in combination were crucial in determining the site of disease, locoregional extent and depth of esophageal wall penetration (T), and any involvement of the mediastinal lymph nodes (N1), extrathoracic lymph nodes (M1) or hepatic metastases. In the locoregional staging of ECC before chemotherapy, we were able to differentiate T2-T3 from T4 in 40 patients; T4 disease was found in 12 potentially resectable cases. We were able to distinguish N0 from N1 in 12 patients. In four cases, the presence of small lymph node and/or liver metastases prompted positioning of an endoprosthesis. The specificity of CT in detecting small lymph nodes in the mediastinum was less than 50% while for CT-PET, it was more than 80%; EUS revealed sensitivity higher than 90% but a low specificity in seven cases. Only CT-PET revealed metastatic subdiaphragmatic lymph nodes (diameter <15 mm) in three cases. Presurgical restaging of the 18 patients (stage III) who had chemotherapy was based on endoscopy, EUS, CT of the chest and abdomen and CT-PET (only in suspected cases) and was compatible with surgery. Anastomotic recurrence was diagnosed in 16 patients by endoscopy with associated biopsy; any intramediastinal spread from anastomotic recurrences was evaluated by chest CT, and CT-PET in suspected cases. CONCLUSIONS: X-ray of the upper digestive tract and chest and abdomen CT scan are useful in preliminary evaluation of ECC. Endoscopy is particularly indicated for evaluating tumour morphology, taking biopsies for a histological diagnosis and the early diagnosis of anastomotic recurrences. EUS is indicated mainly for evaluating T stage before and after chemotherapy or chemoradiotherapy. CT-PET is extremely useful in identifying small mediastinal metastatic lymph nodes (N1) or extrathoracic lymph nodes (M1) and hepatic metastases (</=1 cm), which may escape multislice CT. PET alone is useful for identifying residual or recurrent tumour in the esophageal wall when an endoprosthesis is in place.

Adult↗

PubMed1994

Integrating human brain maps.

Perception, action, cognition, and emotion can now be mapped in the brain by a growing family of techniques. Positron emission tomography, functional magnetic resonance imaging, event-related electrical potentials, event-related magnetic fields, and other non-invasive imaging techniques are rapidly evolving and providing an increasingly rich literature on the functional organization of the human brain. Although no two techniques map identical physiological processes or physical parameters, replications of functionally specific maps by different techniques indicate sufficient common ground for multimodality integration. The process of integration is multi-tiered. Recent advances in integration range from simple image fusion, to model-based synthetic analyses, to collective databases for neural-system modeling. Spatially, temporally, physiologically, and cognitively accurate computational models of the neural systems of human behavior are the ultimate objective of functional brain mapping. This objective will be reached only through integrating the diversity of modern brain-mapping methods.

Brain Mapping↗

PubMed2025

EWS::WT1 Isoform-Dependent Regulation of Neogenes in Desmoplastic Small Round Cell Tumors.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma characterized by the pathognomonic EWS::WT1 fusion protein (FP), an oncogenic chimeric transcription factor (OCTF) resulting from the t(11;22)(p13;q12) translocation. Recent studies have identified "neogenes" (NGs), genes normally silent in normal tissues but transcriptionally activated by OCTFs, as potential tumor-specific markers in fusion-driven cancers. In this study, we investigated the expression and regulation of DSRCT-specific NGs (DSRCT_NGs) using multimodal data across different cohorts of patients, PDX, and cell line data. We evaluated bulk and single-nucleus RNA sequencing of patient specimens from MD Anderson Cancer Center, revealing the robust ability for DSRCT_NGs to distinguish FP-positive DSRCT from samples failing detection of the EWS::WT1 FP. To elucidate the regulatory role of the EWS::WT1 FP in driving NG expression, we performed knockdown experiments in four DSRCT cell lines. This consistently resulted in a reduction of DSRCT_NG expression. Isoform-specific expression of EWS::WT1 in LP9 and MeT-5A mesothelial cells revealed that the E-KTS isoform of EWS::WT1 predominantly drives DSRCT_NG expression. Mechanistically, ATAC-seq and ChIP-seq analyses demonstrated that EWS::WT1 directly binds to accessible chromatin regions near NG transcription start sites, enriched for WT1 motifs and active histone marks. Integration of Hi-ChIP data further revealed that EWS::WT1 facilitates long-range enhancer-promoter looping at DSRCT_NG loci, promoting the expression of nearby genes. Collectively, these findings establish DSRCT_NGs as direct transcriptional outputs of the EWS::WT1 FP and implicate their loci as regulatory regions of the DSRCT transcriptome. Their fusion-dependent expression, chromatin accessibility, and promoter-enhancer connectivity underscore their potential utility as highly specific biomarkers and therapeutic targets in DSRCT.

DSRCT↗

PubMed2006

Correction of an image size difference between positron emission tomography (PET) and computed tomography (CT) improves image fusion of dedicated PET and CT.

AIM: Clinical work in software positron emission tomography/computed tomography (PET/CT) image fusion has raised suspicion that the image sizes of PET and CT differ slightly from each other, thus rendering the images suboptimal for image fusion. The aim of this study was to evaluate the extent of the relative image size difference between PET and CT and the impact of the correction of this difference on the accuracy of image fusion. METHODS: The difference in real image size between PET and CT was evaluated using a phantom study. Subsequently, 13 patients with cancer in the head/neck area underwent both CT and [(18)F]fluorodeoxyglucose PET in a custom-made mask for external beam radiotherapy, with multimodality markers for positional reference. The image size of PET relative to CT was determined by evaluating the distances between the markers in multiple directions in both scans. Rigid-body image fusion was performed using the markers as landmarks, with and without correction of the calculated image size difference. RESULTS: Phantom studies confirmed a difference in real image size between PET and CT, caused by an absolute error in PET image size calibration. The clinical scans demonstrated an average relative difference in image size of 2.0% in the transverse plane and 0.8% along the longitudinal axis, the PET images being significantly smaller. Image fusion using original images demonstrated an average registration error of 2.7 mm. This error was decreased to 1.4 mm after size correction of the PET images, a significant improvement of 48% (P<0.001). CONCLUSIONS: A significant deviation in PET image size may occur, either as a real image size deviation or as a relative difference from CT. Although possibly not clinically relevant in normal diagnostic procedures, correction of such a difference benefits image fusion accuracy. Therefore, it is advisable to calibrate the PET image size relative to CT before performing high-accuracy rigid-body image fusion.

Algorithms↗

PubMed2005

Multimodal genetic diagnosis of solid variant alveolar rhabdomyosarcoma.

The most common types of rhabdomyosarcoma (RMS) are alveolar RMS (ARMS), which are characterized by the specific translocation t(2;13)(q35;q14) or its rarer variant, t(1;13)(p36;q14), producing the fusion genes PAX3-FKHR and PAX7-FKHR, respectively, and embryonal RMS (ERMS), which is characterized by multiple numeric chromosome changes. A solid variant of ARMS that is morphologically indistinguishable from ERMS has been described recently. We present two cases with an initial histopathologic diagnosis of ERMS in which the combined findings by cytogenetic, reverse-transcriptase polymerase chain reaction (RT-PCR), and comparative genomic hybridization (CGH) analyses demonstrate that both tumors were in fact the solid variant of ARMS. The cytogenetic analysis of patient 1 revealed a t(2;13)(q35;q14) and the RT-PCR study detected the corresponding PAX3-FKHR chimeric transcript. In patient 2, the cytogenetic finding of multiple trisomies was compatible with the initial histopathologic diagnosis of ERMS, but the finding of a PAX7-FKHR fusion transcript by RT-PCR pointed to the diagnosis of ARMS. Interestingly, the CGH findings of this case reconciled the molecular and cytogenetic data by detecting, in addition to the trisomies, amplification of chromosomal bands 1p36 and 13q14, where the PAX7 and FKHR genes are located, respectively. Our data indicate that this multimodal genetic analysis could be important for the differential diagnosis of these tumors. Furthermore, our findings and previous studies indicate that there are no apparent genetic differences between solid variant and typical ARMS.

Base Sequence↗

PubMed2004

Implementation of T2*-weighted MR for multimodal image guidance in cerebral cavernomas.

The aim of this study was to evaluate the feasibility, the safety, and the usefulness of T2*-weighted magnetic resonance (MR) for neuronavigational guidance in patients with cerebral cavernomas. Eight patients with intracerebral cavernomas were operated assisted by T2*-weighted MR image-guidance. The cavernomas were either deep-seated or in eloquent regions. Image fusion of a contrast-enhanced T1-weighted gradient-echo (GRE) sequence with a T2*-weighted GRE sequence was performed via an automated fusion software (StealthMerge). The T2*-weighted images were used to secure complete resection of the cavernoma in all patients and to verify resection of surrounding hemosiderin-stained tissue in epilepsy cases. Furthermore, the multimodal neuronavigational concept included ultrasonography, corticography, and evoked potentials. Postoperative MR excluded any residual malformation in all cases. There was no postoperative morbidity; all epilepsy patients are seizure-free up to now. In our preliminary series, T2*-GRE-guided neuronavigation proved useful for resection control in cavernoma surgery, and we suppose that it will be helpful to clarify the discussion on the value of resection of the surrounding hemosiderin-stained tissue.

Adolescent↗

PubMed2026

Breast Cancer Recurrence Status Assessment in 5 Years Using Multimodal Integrated Learning: A Feasibility Study.

Despite advances in breast cancer detection and treatment, recurrence after curative therapy continues to impact long-term survival and quality of life. Therefore, early identification of high-risk patients is crucial to guide personalized treatment and follow-up strategies. Although genomic assays provide valuable prognostic insights, their high cost and limited accessibility hinder widespread adoption in clinical practice. Recent machine learning or deep learning approaches leveraging clinical, imaging, or multimodal data have shown promise but do not reflect real-world clinical scenarios. This study proposes a deep learning-based multimodal framework for predicting 5-year breast cancer recurrence using routinely collected clinical data. The framework consists of three main components. First, we adopted automated tumor segmentation with MedSAM to extract the tumor region from ultrasound images. The radiomics features are extracted from those tumor regions. Second, report features are extracted using a Med-Contrastive Pre-trained Transformers (MedCPT)-based approach incorporating predefined, clinically informed queries. Third, a multimodal integration model jointly processes image, radiomics, clinical features, and report features through modality-specific branches. The image branch employs the Ultrasound Foundation Model (USFM) as the backbone, while structured tabular data is processed using the FT-Transformer architecture. The features of all branches are fused using a mixture-of-experts (MoE)-based classifier, and the entire model is trained using a progressive fusion training strategy. Experimental results confirm the feasibility of using ultrasound images with tumor mask integration for recurrence prediction and demonstrate the additive value of integrating multiple data modalities through the proposed multimodal integration model. The final model for recurrence prediction achieved an AUC of 0.7540, accuracy of 74.61%, sensitivity of 70.41%, and specificity of 76.44%. This feasibility study's findings underscore the potential of the proposed multimodal deep learning framework to provide accessible, accurate, and generalizable recurrence risk prediction using routinely available clinical data, potentially supporting more informed treatment decisions and personalized post-treatment monitoring in real-world clinical practice.

Breast cancer recurrence↗

PubMed2005

Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy.

PURPOSE: To develop a valid treatment strategy for recurrent high-grade gliomas using stereotactic hypofractionated reirradiation based on biologic imaging and temozolomide. PATIENTS AND METHODS: The trial included a total of 44 patients with recurrent high-grade gliomas (1 patient with anaplastic oligodendroglioma, 8 with anaplastic astrocytoma, 33 with glioblastoma multiforme, and 2 with gliosarcoma) after previous surgery and postoperative conventional radiotherapy +/- chemotherapy. For fractionated stereotactic radiotherapy (SFRT) treatment planning, the gross tumor volume was defined by (11)C-methionine positron emission tomography (MET-PET) or (123)I-alpha-methyl-tyrosine (IMT) single-photon computed emission tomography (SPECT)/computed tomography (CT)/magnetic resonance imaging (MRI) fusion in 82% of the patients and by CT/T1+gadolinium-MRI image fusion in 18% of the patients. Six fractions of 5 Gy were administered in 6 days. In 29 of 44 patients (66%), chemotherapy with temozolomide (200 mg/m(2) body surface/day) was given in one to two cycles before and four to five cycles after SFRT. The patients were evaluated in follow-up by clinical investigators and MRI or CT every 3 months after SFRT until death. In cases suspicious for radiation necrosis, a MET-PET or IMT-SPECT investigation was performed. RESULTS: The median survival time in the whole group was 8 months. Treatment planning based on PET(SPECT)/CT/MRI imaging was associated with improved survival in comparison to treatment planning using CT/MRI alone: median survival time 9 months vs. 5 months (p = 0.03, log-rank). Median survival time were 11 months for patients who received SFRT based on biologic imaging plus temozolomide and significantly lower, 6 months for patients treated with SFRT without biologic imaging, without temozolomide or without both (p = 0.008, log rank). The most important prognostic factor in univariate analysis was a long interval between initial diagnosis and recurrence (p = 0.0002, log-rank). In the multivariate model, time interval to retreatment (p = 0.006) and temozolomide (p = 0.04) remained statistically significant. No acute neurologic toxicity Grade 3 or higher and no Grade 4 hematologic toxicity was observed. CONCLUSION: This is the first study of biologic imaging optimized SFRT plus temozolomide in recurrent high-grade gliomas. It demonstrates the feasibility and safety of this approach. The most striking result of the trial is the statistically significant longer survival time in the univariate analysis for patients reirradiated using MET-PET or IMT-SPECT/CT/MRI image fusion in the treatment planning, in comparison to patients treated based on MRI/CT alone. Multivariate analysis confirmed a significant survival benefit from multimodal treatment (i.e., addition of temozolomide), despite the limited number of patients. Whether treatment planning with SPECT/PET independently influences survival has to be studied in a larger series of patients.

Adult↗

PubMed2004

A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging.

Two genetic reporter systems were developed for multimodality reporter gene imaging of different molecular-genetic processes using fluorescence, bioluminescence (BLI), and nuclear imaging techniques. The eGFP cDNA was fused at the N-terminus with HSV1-tk cDNA bearing a nuclear export signal from MAPKK (NES-HSV1-tk) or with truncation at the N-terminus of the first 45 amino acids (Delta45HSV1-tk) and with firefly luciferase at the C-terminus. A single fusion protein with three functional subunits is formed following transcription and translation from a single open reading frame. The NES-TGL (NES-TGL) or Delta45HSV1-tk/GFP/luciferase (Delta45-TGL) triple-fusion gene cDNAs were cloned into a MoMLV-based retrovirus, which was used for transduction of U87 human glioma cells. The integrity, fluorescence, bioluminescence, and enzymatic activity of the TGL reporter proteins were assessed in vitro. The predicted molecular weight of the fusion proteins (~130 kDa) was confirmed by western blot. The U87-NES-TGL and U87-Delta45-TGL cells had cytoplasmic green fluorescence. The in vitro BLI was 7- and 13-fold higher in U87-NES-TGL and U87-Delta45-TGL cells compared to nontransduced control cells. The Ki of (14)C-FIAU was 0.49+/-0.02, 0.51+/-0.03, and 0.003+/-0.001 ml/min/g in U87-NES-TGL, U87-Delta45-TGL, and wild-type U87 cells, respectively. Multimodality in vivo imaging studies were performed in nu/ nu mice bearing multiple s.c. xenografts established from U87-NES-TGL, U87-Delta45-TGL, and wild-type U87 cells. BLI was performed after administration of d-luciferin (150 mg/kg i.v.). Gamma camera or PET imaging was conducted at 2 h after i.v. administration of [(131)I]FIAU (7.4 MBq/animal) or [(124)I]FIAU (7.4 MBq/animal), respectively. Whole-body fluorescence imaging was performed in parallel with the BLI and radiotracer imaging studies. In vivo BLI and gamma camera imaging showed specific localization of luminescence and radioactivity to the TGL transduced xenografts with background levels of activity in the wild-type xenografts. Tissue sampling yielded values of 0.47%+/-0.08%, 0.86%+/-0.06%, and 0.03%+/-0.01%dose/g [(131)I]FIAU in U87-NES-TGL, U87-Delta45-TGL, and U87 xenografts, respectively. The TGL triple-fusion reporter gene preserves the functional activity of its subunits and is very effective for multimodality imaging. It provides for the seamless transition from fluorescence microscopy and FACS to whole-body bioluminescence imaging, to nuclear (PET, SPET, gamma camera) imaging, and back to in situ fluorescence image analysis.

Animals↗

PubMed2026

First-in-Class Small Molecule Inhibitor of Oncogene AVIL in Glioblastoma.

Glioblastoma multiforme (GBM) is the most prevalent and aggressive malignant primary brain tumor, marked by rapid growth, extensive invasiveness, and a median survival of only ∼15 months despite current multimodal therapy. To identify new therapeutic vulnerabilities, we investigated the actin-regulatory protein AVIL, previously implicated through a MARS-AVIL gene fusion in rhabdomyosarcoma. Comprehensive genomic and transcriptomic analyses across REMBRANDT, TCGA, and CGGA datasets revealed recurrent AVIL amplification and consistently elevated AVIL expression in GBM compared with normal brain tissue. AVIL was overexpressed across all GBM molecular subtypes and glioma stem cell (GSC) states but was nearly undetectable in normal astrocytes, neural stem cells, and brain tissues. Functional studies demonstrated that AVIL is both necessary and sufficient for glioma genesis: AVIL silencing eradicated GBM cells in vitro and suppressed xenograft growth in vivo, while AVIL overexpression enhanced proliferation, migration, and transformation. Mechanistically, AVIL drives tumor progression through actin cytoskeleton remodeling and activation of the FOXM1-LIN28B oncogenic pathway. Using a small molecule microarray screen, we identified a selective AVIL-binding compound (compound A) that potently inhibited GBM cell growth with minimal toxicity to normal astrocytes. Gene expression changes induced by compound A mirrored those following AVIL knockdown, indicating on-target activity. Compound A demonstrated robust antitumor efficacy in multiple preclinical GBM models, including orthotopic xenografts, GSC-derived tumors, patient-derived xenografts, and temozolomide-resistant GBM with favorable pharmacokinetics and blood-brain barrier penetration. The minimal AVIL expression in normal tissues and lack of phenotype in AVIL-deficient mice underscore its potential as a low-toxicity therapeutic target. Together, these findings establish AVIL as a critical oncogenic driver in GBM and introduce a first-in-class AVIL inhibitor with strong translational promise for precision neuro-oncology.

Glioblastoma↗

PubMed2003

Direct repair of the pars interarticularis for spondylolysis and spondylolisthesis.

Spondylolysis and spondylolisthesis can be associated with significant low back pain, especially in physically active adolescents. Non-operative management is usually successful in improving symptoms, but surgical intervention is occasionally required for those that fail reduction of activity and bracing. In a subpopulation of these patients, direct repair of the pars interarticularis defect can be an effective modality of treatment. The advantage of direct pars repair over intertransverse fusion with or without segmental instrumentation is the preservation of the anatomic integrity and motion of the affected segment. We describe our experience in 5 patients (aged 15-18 years) managed by direct pars interarticularis repair after failing multimodality non-operative treatment. The length of stay averaged 3.2 days (range 3-4 days). All 5 patients were able to return to full activity with either no (60%) or minor (40%) symptoms. No immediate or delayed complications were noted. Patients were followed a minimum of 30 months (range 30-78 months). All 5 patients demonstrated evidence of bony fusion by radiographic criteria. This demonstrates that direct pars repair is a safe and effective modality to treat select groups of patients with spondylolysis and low-grade spondylolisthesis.

Adolescent↗

PubMed2005

Multistep and multimode cortical anchoring of tea1p at cell tips in fission yeast.

The fission yeast cell-polarity regulator tea1p is targeted to cell tips by association with growing microtubule ends. Tea1p is subsequently anchored at the cell cortex at cell tips via an unknown mechanism that requires both the tea1p carboxy-terminus and the membrane protein mod5p. Here, we show that a tea1p-related protein, tea3p, binds independently to both mod5p and tea1p, and that tea1p and mod5p can also interact directly, independent of tea3p. Despite their related structures, different regions of tea1p and tea3p are required for their respective interactions with an essential central region of mod5p. We demonstrate that tea3p is required for proper cortical localization of tea1p, specifically at nongrowing cell tips, and that tea1p and mod5p are independently required for tea3p localization. Further, we find that tea3p fused to GFP or mCherry is cotransported with tea1p by microtubules to cell tips, but this occurs only in the absence of mod5p. These results suggest that independent protein-protein interactions among tea1p, tea3p and mod5p collectively contribute to tea1p anchoring at cell tips via a multistep and multimode mechanism.

Cell Polarity↗

PubMed2001

Molecular characterization of genomic AML1-ETO fusions in childhood leukemia.

T(8;21) AML1(CBFA2)-ETO(MTG8) is the most common chromosomal translocation in acute myeloid leukemia (AML) in both children and adults. We sought to understand the structure and gain insight into the fusion process between AML1 and ETO by sequencing genomic fusions in 17 primary childhood AMLs and two cell lines with t(8;21). Reciprocal translocations were sequenced for seven of the 19 samples. We assumed a null hypothesis that the translocation breakpoints would be evenly distributed along the intronic breakpoint cluster regions. Testing for multimodality via smoothed bootstrap statistical methods suggested, however, the presence of two separate cluster regions within both the AML1 and ETO breakpoint cluster regions. ETObreakpoints were predominantly located in intron 1B in a defined cluster 5' of exon 1A (scan statistic P value = 0.00001). All patients with available RNA expressed an AML1-ETO mRNA fusion between exon 5 of AML1 and exon 2 of ETO. Since the structural restraints for the fusion protein of AML1-ETO exclude exon 1A, we reason that ETO intron 1B harbors a structural feature with propensity for breakage and/or recombination. Chromosomal breakpoints displayed evidence of fusion by a non-homologous end joining process, with microhomologies and nontemplate nucleotides at some fusion junctions. Breakpoints in general displayed similar complexity of duplications, deletions, and insertions to other common pediatric leukemia translocations (TEL-AML1, MLL-AF4, PML-RARA, CBFB-MYH11) that we and others have analyzed.

Acute Disease↗

PubMed2006

SPECT-CT fusion: a new diagnostic tool for endocrinology.

INTRODUCTION: The introduction of the DICOM format in all diagnostic imaging devices allowed co-registering SPECT, CT, MR and other types of biomedical imaging. Fusion can be performed by dedicated hybrid devices or by means of software. The fusion algorithm consists of two steps: coregistration and simultaneous visualization. Our center gradually implemented SPECT-CT fusion in clinical diagnostic work-up of several endocrinologic and oncologic diseases more than 2 years ago. MATERIAL AND METHODS: An easy and fast algorithm in terms of computational complexity of image fusion was presented and applied to 81 consecutive cases. Thirty-two patients were scheduled to SPECT-CT fusion after thyroidectomy and (131)I treatment for thyroid cancer, twelve after somatostatin receptor scintigraphy, seven after 131I MIBG therapy, six after diagnostic MIBG scintigraphy with (123)I or (131)I, three after parathyroid scintigraphy and two after bone scan. The most common indication to the fusion was the need of metabolic characterization of suspected lesions detected on CT scan. The anatomic localization of a focal uptake seen on SPECT and the evaluation of the radiometabolic therapy effect folloved. RESULTS: A variance of error level observed was a result of human factor, decision on marker's placement, respiratory movements and marker's displacement between acquisitions. However, 74% of patients in our series have fusion results classified as "very good" or "good". CONCLUSIONS: The selection of patients, the training of the personel and the cooperation with radiologists are the most important factors for a correct application and interpretation of the SPECT-CT image fusion.

Algorithms↗

PubMedDate not supplied

Congenital tarsal coalition: multimodality evaluation with emphasis on CT and MR imaging.

Congenital tarsal coalition is a diagnosis that is often overlooked in young patients who first present with foot and ankle pain. Calcaneonavicular and talocalcaneal coalitions are encountered most frequently; fusion at other sites is much less common. Tarsal coalitions may be osseous, cartilaginous, or fibrous. Calcaneonavicular coalitions are readily detected on oblique radiographs. Radiographic confirmation of talocalcaneal coalition is more difficult than for fusion at other locations, although several secondary radiographic signs may indirectly suggest the diagnosis. Computed tomography (CT) and magnetic resonance (MR) imaging are invaluable for assessment of tarsal coalitions because they allow differentiation of osseous from nonosseous coalitions and because they depict the extent of joint involvement as well as secondary degenerative changes, features of vital importance in surgical planning. Short-inversion-time inversion recovery MR images may reveal bone marrow edema along the margins of the abnormal articulation, an important clue to the diagnosis. Moreover, CT or MR imaging may be required to confirm the diagnosis of talocalcaneal coalition when radiographic findings are equivocal. Because the diagnosis of tarsal coalition is often not entertained by the clinician ordering a CT or MR imaging examination, multiplanar imaging of the ankle and hindfoot is required.

Adolescent↗

PubMed2005

A biometric identification system based on eigenpalm and eigenfinger features.

This paper presents a multimodal biometric identification system based on the features of the human hand. We describe a new biometric approach to personal identification using eigenfinger and eigenpalm features, with fusion applied at the matching-score level. The identification process can be divided into the following phases: capturing the image; preprocessing; extracting and normalizing the palm and strip-like finger subimages; extracting the eigenpalm and eigenfinger features based on the K-L transform; matching and fusion; and, finally, a decision based on the (k, l)-NN classifier and thresholding. The system was tested on a database of 237 people (1,820 hand images). The experimental results showed the effectiveness of the system in terms of the recognition rate (100 percent), the equal error rate (EER = 0.58 percent), and the total error rate (TER = 0.72 percent).

Algorithms↗

PubMedDate not supplied

Visceral clear cell sarcoma of soft tissue with confirmation by EWS-ATF1 fusion detection.

Clear cell sarcoma of soft tissue (CCS-ST) is a rare malignant neoplasm characterized by a tumor-defining translocation [t(12;22) (q13;q12)], resulting in the EWS-ATF1 gene fusion. An extremely limited number of visceral CCS-ST cases have been reported in the literature. Here the authors report a visceral CCS-ST in a Hispanic adolescent male with a large infiltrative mass involving the small bowel. The tumor was evaluated by light microscopy, immunocytochemistry, electron microscopy, cytogenetics, and molecular genetics. The tumor cells were strongly positive for S-100 protein, but negative for HMB-45. Rare premelanosomes were identified only after an extensive search with electron microscopy. Cytogenetics showed a characteristic t(12;22)(q13;q12) for CCS-ST with isochromosome 18q and trisomy 22. An EWS exon 8 sense primer and an antisense ATF1 primer were employed for detection of the CCS-ST tumor-defining EWS-ATF1 translocation, using reverse transcriptase-polymerase chain reaction techniques (RT-PCR), and the fusion gene breakpoint underwent DNA sequencing. This tumor is exceptional, because it is the first visceral CCS-ST that has been confirmed by RT-PCR and DNA sequencing. This case also illustrates the necessity of a multimodal approach to tumor diagnosis, and the utility of cytogenetics and molecular pathology in confirming the diagnosis of CCS-ST and eliminating conventional metastatic or primary visceral malignant melanoma as a consideration.

Adolescent↗