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Results for “Multimodal Fusion”

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PubMed1988

Studies on the growth of mast cells in rats. Changes in granule size between 1 and 6 months.

Mast cells from rats aged 1 month, 3 months and 5 to 7 months were compared with respect to cell size and secretory granule size and number. With increasing age there was an increase in mean total cell volume accounted for almost entirely by an increase in mean total granule volume/cell even though there was no apparent increase in the number of granules. An increase in histamine content closely paralleled the increase in total granule volume. In each age group, the distribution of equivalent volumes of granule profiles exhibited periodic multimodality consistent with a Poisson distribution of granule volume. We have interpreted these observations in terms of a model in which total granule volume/cell increases through the production of unit granules of uniform size; the increasing size of individual granules we attribute to the fusion of unit granules with each other and with larger granules.

Aging↗

PubMed2006

Visualization of telomerase reverse transcriptase (hTERT) promoter activity using a trimodality fusion reporter construct.

UNLABELLED: Our goal was to noninvasively measure chemotherapy-induced changes in the expression of critical tumor growth genes. To achieve this goal, we used radionuclide and optical methods to measure changes in human telomerase reverse transcriptase (hTERT) gene expression in tumor cells before and after 5-fluorouracil treatment. METHODS: A fusion reporter construct, containing humanized Renilla luciferase (hrl, for bioluminescent imaging), monomeric red fluorescence protein 1 (mrfp1, for fluorescent imaging), and a truncated thymidine kinase (ttk, for imaging of radiolabeled acycloguanosines), was placed under the control of hTERT promoter fragments. These constructs were introduced into tumor cell lines with and without hTERT expression. Transfected cells were treated with 5-fluorouracil, a chemotherapeutic that decreases hTERT gene expression, and treatment-induced changes in hTERT promoter activity were imaged. RESULTS: When the fusion construct is introduced into cell lines that express hTERT, all 3 reporter systems are highly expressed and hTERT promoter activity can be visualized. Cell lines lacking hTERT transcription show no significant reporter expression. Decreases in hTERT gene expression caused by 5-fluorouracil treatment could be visualized in living 293T cells by both fluorescent microscopy and bioluminescent imaging. CONCLUSION: hTERT promoter activity can be monitored by 1 radionuclide and 2 optical reporter systems using a single reporter construct. This in vitro study provides evidence that our multimodality reporter construct can be used to study the expression of a critical tumor growth gene in living subjects.

Antineoplastic Agents↗

PubMed2002

Multimodality management of a giant cell tumor arising in the proximal sacrum: case report.

STUDY DESIGN: Descriptive. OBJECTIVE: To outline a novel multimodality approach for a difficult surgical resection of a giant cell tumor in the cephalad portion of the sacrum. SUMMARY OF BACKGROUND DATA: Giant cell tumors of the sacrum are rare primary bone tumors. Recent reports have demonstrated diminished giant cell tumor recurrence with cryosurgery by using a "direct pour" technique with liquid nitrogen. Although successful in decreasing tumor recurrence, this technique is accompanied by a 4%-8% rate of skin necrosis and high rates of pathologic fracture. The authors describe resection and a novel, controlled method of argon-based cryotherapy (followed by a unique pelvic reconstruction) for a large, difficult giant cell tumor of the sacrum. METHODS: A 29-year-old woman presented with complaints of right foot drop and decreased sensation of the right buttock, posterior thigh, posterior calf, and lateral aspect of the right foot. Radiographic evaluation revealed a mass in the right sacrum; histologic examination of CT-guided biopsy revealed a giant cell tumor. A combined anterior abdominal and posterior sacral approach was performed, the tumor was resected, and the margin of the cavity was treated with controlled argon-based cryotherapy. The combination of thermocouples, electromyographic monitoring, and rapid freeze-thaw cycles allowed a controlled ablation of the tumor margin while ensuring that surrounding structures, such as the rectal wall, sacral nerves, and gluteal muscles, were not damaged. Posterior spinal fusion L4 to sacrum, posterior spinal instrumentation L4 to pelvis, and allograft reconstruction of the right sacrum were performed. RESULTS: The patient recovered well without skin necrosis or pathologic fracture. Urinary and fecal continence were preserved. At the 20-month follow-up the patient has no evidence of local tumor recurrence and is fully ambulatory without a brace or narcotic medication. CONCLUSION: A novel multimodality approach, consisting of resection, controlled cryosurgery, and a unique lumbopelvic reconstruction, was safe and successful in managing a challenging proximal sacral giant cell tumor. Twenty months after surgery the patient has excellent bowel and bladder control, no tumor recurrence, and functional ambulation without a brace or pain.

Adult↗

PubMed1997

Recent and future evolutions in NeuroSPECT with particular emphasis on the synergistic use and fusion of imaging modalities.

Recent and future evolutions in neuroSPECT apply to radiopharmaceuticals techniques and the synergistic use of different imaging modalities in the work-up of neurological disorders. The introduction of Technetium labelled perfusion tracers, which could pass the intact blood-brain barrier, together with the implementation of the tomographic principle, by making the conventional gamma camera rotating, enabled estimation of regional cerebral blood flow and indirectly of local brain metabolism. In addition at present Thallium-201 and Tc-99m sestaMIBI allow functional detection of viable tumor tissue, without interference from previous surgery or radiotherapy as seen using CT-scan or MRI. In neurology this has led to the recognition of SPECT by the American Academy of Neurology (Therapeutics and technology subcommittee) as an established or promising tool in major neurological disorders such as dementia, stroke and epilepsy, while other domains such as brain oncology are considered investigational. With regard to radiopharmaceuticals, recent evolutions mainly include the development of mostly Iodine-123 labelled receptor ligands, some of which are already commercially available. For instrumentation advances consist e.g. of multidetector systems equipped with fanbeam collimators, attenuation and scatter correction or coincidence detection. Given the present role for nuclear neurology it may be expected that these additional radiopharmaceutical and technical innovations will continue to stimulate the development of SPECT of the brain. The synergistic use of several imaging techniques such as CT, (functional) MRI, source imaging, SPECT and PET represents a multimodal holistic approach to probe cerebral functions for research and clinical purposes. Clinical indications, in which this synergistic use is illustrated include e.g. support of the clinical diagnosis of dementia of the Alzheimer type, presurgical ictal detection of seizure focus, detection of acute ischemia and differential diagnosis between radiation necrosis and brain tumor recurrence. The synergistic use of imaging modalities, optimally applied using image fusion, allows to overcome the intrinsic limitations and to enhance the specific advantages of the different approaches as it leads to increased precision and accuracy, as well for spatial anatomofunctional correlation as for quantification.

Alzheimer Disease↗

PubMed2026

A multi-modal survival prediction framework with group-based batch training and structural consistency alignment.

OBJECTIVE: Integrating whole-slide images (WSIs) with transcriptomic profiles is pivotal for enhancing cancer survival prediction. However, the intrinsic gigapixel resolution and variable sequence lengths of WSIs create a fundamental trade-off between training efficiency and the preservation of data heterogeneity in existing frameworks. Furthermore, substantial statistical and structural discrepancies between histological and genomic modalities often impede effective cross-modal alignment and fusion, thereby limiting prognostic accuracy. METHODS: We propose PRISM, an efficient multi-modal learning framework for integrating WSIs with transcriptomic profiles. To reconcile training efficiency with full data heterogeneity, PRISM first stochastically partitions variable-length WSI sequences into a main subset and a complementary residual subset, both of which are packed into fixed-length groups for batch training. The main subset is processed in the main branch, utilizing isolation masking to maintain intra-group sequence independence. Simultaneously, the residual subset is consolidated into "hyperslides" within a residual branch that leverages tailored supervision, effectively capturing inter-slide correlations. Furthermore, PRISM integrates an Informative Token Aggregation (ITA) module to reduce redundancy in WSIs and employs Cross-batch Structural Consistency Alignment (CBSCA) mechanism to enhance inter-modal structural connectivity. Finally, efficient cross-modal feature interaction is achieved through a Low-rank Bilinear Gated Fusion (LBGF) module. Code is available at https://github.com/Alisa2080/PRISM. RESULTS: Compared with existing methods, PRISM achieves the best overall C-index across five TCGA cohorts. On the larger TCGA-BRCA dataset, PRISM requires only 6 hours of training time, substantially reducing computational cost relative to strong multimodal baselines. Furthermore, comprehensive evaluations demonstrate that PRISM achieves the best overall IBS ranking and favorable time-dependent AUC performance at 1, 3, and 5 years, thereby delivering a more favorable trade-off between prognostic performance and computational efficiency. CONCLUSION: PRISM provides a favorable balance between predictive performance, calibration quality, and computational efficiency, highlighting its potential for practical deployment in multimodal survival modeling for computational pathology.

Humans↗

PubMed2004

Hypotension-induced loss of intraoperative monitoring data during surgical correction of scheuermann kyphosis: a case report.

STUDY DESIGN: Presentation of a case report of Scheuermann kyphosis surgical correction. OBJECTIVE: To describe a scenario where both neurogenic mixed evoked potentials and somatosensory-evoked potentials were lost due solely to hypotension before any correction of a kyphotic spinal deformity was performed. SUMMARY OF BACKGROUND DATA: Multimodality intraoperative neurophysiologic monitoring of the spinal cord has become widely utilized during surgical correction of scoliotic and kyphotic deformities. Most spinal surgeries also benefit from a state of hypotension to minimize blood loss, but unchecked and persistent hypotension may lead to inadequate perfusion to the spinal cord, resulting in spinal cord dysfunction noted by diminution of neuromonitoring data. METHODS: An 18-year-old boy with a 95 degrees Scheuermann kyphosis underwent a posterior spinal fusion for correction of his deformity. Intraoperative neurophysiologic monitoring consisting of neurogenic mixed evoked potentials and somatosensory-evoked potentials were performed throughout surgery. RESULTS: After placement of segmental pedicle screw fixation points and multiple osteotomies, before any instrumented correction of the deformity, all lower extremity neuromonitoring data were acutely lost. The surgeon was immediately warned of the data loss, with the mean arterial pressure noted to be 50 mm Hg. The mean arterial pressure was raised with the use of epinephrine bolus and dopamine infusion. Subsequently, all lower extremity neuromonitoring data returned. A Stagnara wake-up test was performed, which the patient passed, and the surgical correction was performed with his pressure maintained on a dopamine infusion. He awakened without neurologic deficits and had an uneventful recovery. CONCLUSIONS: Although a state of mild hypotension may be beneficial to limit blood loss during spinal deformity corrective surgery, acute and/or prolonged hypotension may jeopardize spinal cord vascularity and should be avoided especially during surgical treatment of high-risk deformities such as kyphosis. Early warning by multimodality physiologic neuromonitoring appears to be a useful method to alert surgeons of the potentially devastating problem of hypotension-induced spinal cord dysfunction and allows immediate corrective actions.

Adolescent↗

PubMed2026

Hypernetwork-guided fusion with intra-class MixUp for breast cancer subtyping.

Accurate breast cancer subtyping guides treatment selection, yet histopathology captures morphology without molecular state, while genomic profiling captures molecular signatures without spatial context. Existing fusion methods rely on concatenation, or on attention applied only after each modality is encoded independently. This work identifies a scale-dependent asymmetry in the direction of cross-modal conditioning: the direction that performs best under limited samples is not the one that holds at scale, and the reversal is traced to the capacity of the modulation pathway rather than to the fusion principle. The comparison is carried out within a hypernetwork-guided framework in which an auxiliary network maps one modality to conditioning parameters that modulate the other's feature representation, shaping features at the parametric level rather than the decision stage; modulation is patient-specific rather than patch-specific. Both directions are instantiated-gene-to-image (HyperG2I) and image-to-gene (HyperI2G) - and trained under a label-aware MixUp strategy that interpolates within-class samples across both modalities, preserving the hard binary labels clinical decisions require. The framework is evaluated on two paired TCGA-BRCA cohorts-one limited-sample, one independently assembled at scale-under a single protocol spanning two whole-slide representations, multiple visual backbones, and both conditioning directions. On the limited-sample cohort, gene-to-image conditioning at its optimal augmentation setting exceeds early fusion and both unimodal baselines, giving the highest recall on the aggressive Basal/HER2 class of any configuration evaluated, and an ablation favours intra-class over inter-class mixing. At scale this ordering does not hold: image-to-gene conditioning sustains its performance whereas gene-to-image does not, recovering only partially under the full tissue bag and isolating the capacity of the modulation pathway as the binding constraint. Direction and capacity of cross-modal conditioning, rather than fusion depth alone, therefore govern how such frameworks scale.

Breast Neoplasms↗

PubMed2001

Neuro-fuzzy systems for computer-aided myocardial viability assessment.

This paper describes a multimodality framework for computer-aided myocardial viability assessment based on neuro-fuzzy techniques. The proposed approach distinguishes two main levels: the modality-independent inference level and the modality-dependent application level. This two-level distinction releases the hard constraint of multimodality image registration. An abstract description template is used to describe the different myocardial functions (contractile function, perfusion, metabolism). Parameters extracted from different image modalities are combined to derive a diagnostic image. The neuro-fuzzy techniques make our system transparent, adaptive and easily extendable. Its effectiveness and robustness are demonstrated in a positron emission tomography/magnetic resonance imaging data fusion application.

Artificial Intelligence↗

PubMed2001

[Cytokines: current status and prospects in the treatment of skin tumors].

Various therapeutic options using cytokines have been described in the treatment of melanoma, T cell lymphoma, B cell lymphoma, squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma. The treatment regimens include cytokine substitution, cytokine induction, cytokine transfection and therapeutic cytokine constructs. In the adjuvant treatment of melanomas, IFN-alpha has become well established. Statistical evaluations of different adjuvant trials show that a significant prolongation of recurrence-free intervals can be achieved. IL-2 has a role in the therapy of advanced melanomas as well as in vaccination strategies. Further possible therapeutic immune modulations, which have been evaluated in experimental approaches and pilot studies, include treatment with IL-4, IL-7 and GM-CSF. Treatment with IL-12 promises to open new perspectives. A well established regimen in the treatment of T cell lymphoma stages Ia-IIb is the combination of PUVA and IFN-alpha. In vitro data also indicate an important (patho)physiological role for IL-12, so that this agent has been tested in phase I studies. IL-2, IFN-gamma, and the fused cytokine-toxin molecules DAB389IL-2 offer further therapeutic alternatives. B cell lymphomas are treated with antibody-IL-2 fusion proteins. Advanced or inoperable squamous cell carcinoma and basal cell carcinoma may be treated with local IFN-alpha injections. IFN-alpha or TNF-alpha may be considered for the treatment of recurrent or advanced Merkel cell carcinoma. In dermatological oncology cytokine treatment focuses on melanome an T cell lymphome. Cytokine application is mainly an integral part of multimodal regimens.

Animals↗

PubMed2001

Minimal residual disease in soft-tissue sarcomas.

Soft-tissue sarcomas are characterized by the development of disease recurrence in a distinct subgroup of patients. Despite intense efforts in applying multimodal treatment, the risk of local recurrence or distant metastases remains a considerable threat to patients with soft-tissue sarcoma. This review focuses on the efforts aimed at defining local and systemic tumor extent at the level of minimal residual disease (MRD) tumor cell detection. Examination of MRD in soft-tissue sarcomas has experienced a significant boost from the definition of fusion transcripts resulting from stable chromosomal translocations. The sensitivity and exclusive specificity of the reverse-transcription polymerase chain reaction (RT-PCR) protocols have given insights into tumor cell residues in nearly all body compartments. The accumulated data demonstrates that even after oncologic resections most patients will still harbor a significant tumor burden. Clinical concepts arising out of these new data are under way. One of these concepts is the targeting of the fusion transcript for therapy. However, this approach is still restricted to the experimental setting. The development of clinical applications remains a challenging task, requiring the treatment of as many patients as possible in centers specializing in all of the affected disciplines.

Adult↗

PubMedDate not supplied

Image fusion of computed tomographic and magnetic resonance images for the development of a three-dimensional musculoskeletal model of the equine forelimb.

Biomechanical models that compute the lengths and forces of muscle-tendon units are broadly applicable to the study of factors that promote injury and the planning and effects of orthopedic surgical procedures in equine athletes. A three-dimensional (3D) generic musculoskeletal model of the equine forelimb comprised of bony segment, muscle-tendon, and ligament information, was developed based on high-resolution computed tomographic (CT) and T1-weighted magnetic resonance (MR) images from an isolated forelimb of a Thoroughbred racehorse. Image fusion was achieved through coregistration of CT and MR images with an image analysis program (Analyze) by adjustment of the relative position and orientation of fiducial markers visible in both modalities until the mutual information between the images was maximized. 3D surfaces of the bones and origin/insertion sites, centroid paths and volumes of the muscle-tendon and ligamentous structures were obtained from the multimodal (CT/MR) images using semiautomated and manual segmentation combined with sagittal and transverse color-cryosection anatomic images obtained from three other cadaveric equine forelimbs. Once bony and soft-tissue structures were reconstructed in the same coordinate system, data were imported to a software package for interactive musculoskeletal modeling (SIMM). The combination of integrated CT and MR acquisitions and anatomical images provided an accurate and efficient means of generating a 3D model of the musculoskeletal structures of an average-sized equine adult horse.

Animals↗

PubMed2002

The benefit of neurogenic mixed evoked potentials for intraoperative spinal cord monitoring during correction of severe scoliosis: a case study.

STUDY DESIGN: A case report is presented. OBJECTIVE: To present a case in which surgical correction of a severe scoliotic curve caused unilateral loss of neurogenic mixed evoked potential data despite unchanged somatosensory data. SUMMARY OF BACKGROUND DATA: Surgical correction of large scoliotic curves presents a risk to the function of the spinal cord. Multimodality intraoperative neurophysiologic monitoring of the spinal cord is recommended during such procedures. METHODS: A 13-year-old girl with severe double major scoliosis underwent a staged operative procedure for correction of her spine deformity. Intraoperative neurophysiologic monitoring using somatosensory-evoked potentials and neurogenic mixed evoked potentials was performed for each stage. RESULTS: During the final stage (a T4-L5 posterior instrumentation and fusion) left neurogenic mixed evoked potential data were lost approximately 45 minutes after placement of the left-side, correcting rod. The surgeon was warned of the data change. Set bolts were loosened at all fixation points, and the data quickly returned to within normal limits of baseline. Somatosensory data never approached warning criteria at any point during surgery. The patient awakened with no neurologic deficit. CONCLUSIONS: Neurophysiologic monitoring using both somatosensory-evoked potentials and neurogenic mixed evoked potentials is recommended when surgery is performed to correct spine deformity. The Stagnara wake-up test, somatosensory-evoked potentials, and neurogenic mixed evoked potentials are important components of spinal cord monitoring during surgery, and should be used together for optimal protection of neurologic function.

Adolescent↗

PubMed2003

Management of the cervical esophagus and hypofarinx perforations complicating anterior cervical spine surgery.

STUDY DESIGN: Five cases of esophageal or pharyngeal perforation diagnosed during or after anterior cervical spine surgery are presented. OBJECTIVE: To outline a protocol for the early diagnosis and treatment of iatrogenic pharyngoesophageal perforations. SUMMARY OF BACKGROUND DATA: Pharyngoesophageal perforations after anterior cervical spine surgery are uncommon or rarely reported complications. They may have serious functional consequences, including death, if they are not diagnosed promptly and treated effectively. These potentially fatal conditions require a surgical and medical therapy. METHODS: Clinical course, diagnostic tools and guidelines for the management of five patients presenting esophagopharingeal perforations are illustrated. RESULTS: These five cases resulted in definitive healing of the laceration without functional consequences. CONCLUSION: We believe that awareness of these complications and their causes, prompt recognition of the symptoms and immediate and multimodality therapies are essential tools to achieve successful results.

Bone Screws↗

PubMed1987

Defective cytoplasmic granule formation. I. Abnormalities affecting tissue mast cells and pancreatic acinar cells of beige mice.

Beige mice (C57BL/6-bgJ/bgJ) express the Chediak-Higashi syndrome, a genetically determined constellation of morphologic and functional abnormalities affecting cells that synthesize cytoplasmic granules; a similar disorder also occurs in humans and several other mammalian species. We used a computer-assisted morphometric approach to identify and quantitate the effect of the beige mutation on the structure of mast cell or pancreatic acinar cell cytoplasmic granules. Beige and control mouse mast cell or pancreatic acinar cell granules exhibited periodic, multimodal distributions of equivalent volumes in which the modes fell at volumes that were integral multiples of the volume of the "unit granule," whose volume (the "unit volume" or v1) was defined by the first mode in the granule equivalent volume distribution. But the modal frequency of the C57BL/6-bgJ/bgJ mast cell granule equivalent volume distribution fell at v1, a pattern consistent with a haphazard pattern of "unit granule" fusion, whereas the corresponding modal frequency for the control mast cell granules fell at v3, a pattern consistent with a "unit addition" model of granule fusion. In addition, the unit volume of beige mouse mast cell granules was 18 times that of control mouse mast cell granules. By contrast, the unit volume of beige mouse pancreatic acinar cell granules was only slightly (23%) greater than that of control cells. C57BL/6-bgJ/bgJ and control cells did not differ significantly in total cell or nuclear volume, or in the aggregate volume of their cytoplasmic granules. However, C57BL/6-bgJ/bgJ mast cells or pancreatic acinar cells contained significantly fewer granules than did their normal counterparts. These findings are consistent with the hypothesis that the beige mutation affects the formation of unit granules and also alters the pattern of aggregation and fusion of unit granules. The data also identify quantitative differences in the expression of the beige mutation in mast cells and pancreatic acinar cells.

Animals↗

PubMedDate not supplied

A positron-emitting internal marker for identification of normal tissue by positron emission tomography: phantom studies and validation in patients.

PURPOSE: This study evaluated in a phantom model and verified in patients with lung cancer whether the use of an internal positron-emitting labeled marker could localize a critical structure by positron emission tomography (PET) imaging and verify multimodality image registration. MATERIALS AND METHODS: An initial device and method were developed to demonstrate by dedicated PET the location of the normal esophagus in a phantom and in three patients using a column of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) solution between proximal and distal gas phases in polyurethane tubing. The device was assessed for possible loss of radioactivity. PET, CT and PET-CT fusion imaging followed. RESULTS: X-rays of the marker device showed a continuous fluid column. No leakage of contents was detected. The internal marker in the phantom and in patients allowed visualization by PET of the esophagus, and verified an image registration algorithm. CONCLUSIONS: A positron-emitting internal marker was constructed, demonstrated to retain tracer, and shown to be capable of verifying an image registration algorithm and identifying a critical structure, the esophagus, by PET in a phantom and in patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

PET/CT image navigation and communication.

UNLABELLED: The advent of multimodality imaging scanners combining PET and CT has led to a new paradigm in image display and presentation that raises new challenges in workstation interpretation software, image navigation, and communication. The essence of multimodality imaging is the ability to overlay imaging information from different modalities in a visually compelling fashion. This is accomplished by combining functional and anatomic data into multidimensional views using color-encoding techniques that provide visual clues on the spatial distribution of image data. DISCUSSION: Combined PET/CT scanners provide spatially registered images from the two modalities acquired simultaneously in a single imaging session. Special reconstruction software and image display programs are required to rescale the native images from different spatial resolution into orthogonal or oblique reformatted planes in which data from PET images are color coded and superimposed on corresponding anatomic CT images. The color overlay technique allows the user to visually identify areas of high tracer activity and determine the underlying anatomic structure. Because of the multidimensional nature of the data, visualization requires interactive multidimensional navigation techniques that allow the viewer to move the visualization planes through three spatial directions and two additional dimensions. The fourth dimension is the continuum blend from PET to CT fusion, and the fifth is the dynamic range of the CT images that can be adjusted to display different tissue characteristics, such as bones, soft tissue, and lungs. Software tools currently available are often relatively complex, requiring the user to perform cumbersome maneuvers and time-consuming image manipulation to navigate through all dimensions and obtain adequate image settings and plane positioning for diagnostic interpretation of the image data. Moreover, the ability to convey these images to referring physicians is usually limited because of the lack of adequate viewing software. Distribution of results is usually performed instead through static "snapshots" of the fused images generated by the interpreting radiologist. The ability of the referring physician to navigate through the set of multimodality image data is thus limited. CONCLUSION: The wider adoption of multimodality PET/CT imaging techniques in routine clinical use will depend heavily on the development of more adequate image display and navigation tools that allow interpreting physicians to navigate easily and efficiently through multiple dimensions of data. Distribution of results to referring physicians and care providers also requires new tools for interactively reviewing the multimodality data, and current static images obtained from fused image data remain inadequate for proper visualization of the true content of images.

Algorithms↗

PubMedDate not supplied

Second-generation triple reporter for bioluminescence, micro-positron emission tomography, and fluorescence imaging.

Bioluminescence, positron emission tomography (PET), and fluorescence modalities are currently available for noninvasive imaging in vivo, each with its own merits. To exploit the combined strengths of each and facilitate multimodality imaging, we engineered a dual-reporter construct in which firefly luciferase (FLuc) and a 12-amino acid nonstructural linker were fused in frame to the N-terminus of a mutant herpes simplex virus thymidine kinase (mNLS-SR39TK) kinetically enhanced for positron emission tomography (PET). Furthermore, a triple-reporter construct was developed in which monster green fluorescent protein (MGFP), a recently available enhanced fluorescent protein, was introduced into the fusion vector downstream of an internal ribosome entry site (IRES) to allow analysis by fluorescence microscopy or flow cytometry without compromising the specific activities of the upstream fusion components. FLuc bioluminescence was measured with a cooled charge-coupled device camera and mNLS-SR39TK activity by 9-[4-[(18)F]fluoro-3-(hydroxymethyl) butyl guanine ((18)F-FHBG) microPET or (3)H-penciclovir net accumulation. Importantly, HeLa cells transiently transfected with the FLuc-mNLS-SR39TK-IRES-MGFP triple reporter retained the same specific activities of the FLuc-mNLS-SR39TK heteroenzyme and the individual unfused enzymes with no change in protein half-lives. The presence of the IRES-MGFP modestly decreased upstream heteroprotein expression. In living mice, somatic gene transfer of a ubiquitin promoter-driven FLuc-mNLS-SR39TK-IRES-MGFP plasmid showed a > 1,000-fold increase in liver photon flux and a > 2-fold increase in liver retention of (18)F-FHBG by microPET compared with mice treated with control plasmid. Multifocal hepatocellular fluorescence was readily observed by standard confocal microscopy. This second-generation triple reporter incorporating enhanced components enables bioluminescence, PET, and fluorescence imaging of cells and living animals.

Acyclovir↗

PubMed2006

[Lumbar spinal stenosis].

Lumbal spinal stenosis is gaining more and more clinical relevance because of changing population structure and increasing demand on lifequality in the elderly. Current treatment recommendations are based on clinical experience, expert opinions and single studies rather than on proven evidence. The radiologic degree of stenosis does not correlate with the patients' clinical situation. It is not the main factor indicating surgery but rather the typical history and spinal claudication. Symptomatic patients with light to moderate complaints should undergo multimodal conservative treatment. Epidural injections, delordosating physiotherapy and medication are useful. In patients with severe symptomatic stenosis surgery is indicated after a conservative treatment of 3 months. Relevant pareses or a cauda equina syndrome are absolute indications for surgery. The general aim is to decompress sufficiently while maintaining or restoring segmental stability. A laminectomy is not necessarily required. In patients with accompanying degenerative Meyerding grade I-II spondylolisthesis or instability in functional radiographs, fusion or dynamic stabilisation are recommended in addition to decompression, depending on the patient's age and activity level.

Decompression↗