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1.
Clin Plast Surg ; 47(2): 245-259, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32115050

RESUMO

Nerve imaging is an important component in the assessment of patients presenting with suspected peripheral nerve pathology. Although magnetic resonance neurography and ultrasound are the most commonly utilized techniques, several promising new modalities are on the horizon. Nerve imaging is useful in localizing the nerve injury, determining the severity, providing prognostic information, helping establish the diagnosis, and helping guide surgical decision making. The focus of this article is imaging of damaged nerves, focusing on nerve injuries and entrapment neuropathies.

2.
Clin J Sport Med ; 30(1): e11-e14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30908328

RESUMO

A 61-year-old man presented with chronic dorsal foot pain of 9 years that worsened with ambulation. Conventional diagnostic imaging and medical workup were unrevealing, and ankle arthrodesis had been recommended by an orthopedic surgeon for pain relief. Instead, the patient participated in a clinical imaging trial designed for identifying pain generators using whole-body fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). The scan revealed not only high 18F-FDG uptake at the site of pain, but also a hematoma and an inflamed, fibrotic, ruptured plantaris muscle. The fibrotic plantaris likely altered biomechanics with walking, explaining why symptoms worsened with activity. A simple tenotomy of the plantaris tendon was performed to decouple ankle movement from the plantaris injury, resulting in pain relief. This case illustrates the potential of whole-body 18F-FDG PET/MRI to better localize pain generators.

3.
J Pain Res ; 11: 2353-2357, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349360

RESUMO

Background: The ability to accurately diagnose and objectively localize pain generators in chronic pain sufferers remains a major clinical challenge since assessment relies on subjective patient complaints and relatively non-specific diagnostic tools. Developments in clinical molecular imaging, including advances in imaging technology and radiotracer design, have afforded the opportunity to identify tissues involved in pain generation based on their pro-nociceptive condition. The sigma-1 receptor (S1R) is a pro-nociceptive receptor upregulated in painful, inflamed tissues, and it can be imaged using the highly specific radioligand 18F-FTC-146 with PET. Case presentation: A 50-year-old woman with a 7-year history of refractory, left-knee pain of unknown origin was referred to our pain management team. Over the past several years, she had undergone multiple treatments, including a lateral retinacular release, radiofrequency ablation of a peripheral nerve, and physical therapy. While certain treatments provided partial relief, her pain would inevitably return to its original state. Using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with the novel radiotracer 18F-FTC-146, imaging showed increased focal uptake of 18F-FTC-146 in the intercondylar notch, corresponding to an irregular but equivocal lesion identified in the simultaneously acquired MRI. These imaging results prompted surgical removal of the lesion, which upon resection was identified as an inflamed, intraarticular synovial lipoma. Removal of the lesion relieved the patient's pain, and to date the pain has not recurred. Conclusion: We present a case of chronic, debilitating knee pain that resolved with surgery following identification of the pathology with a novel clinical molecular imaging approach that detects chronic pain generators at the molecular and cellular level. This approach has the potential to identify and localize pain-associated pathology in a variety of chronic pain syndromes.

4.
J Neuroinflammation ; 15(1): 55, 2018 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-29471880

RESUMO

BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin. Control mice received CFA emulsion and pertussis toxin without MOG peptide, while a separate cohort of naïve mice received no treatment. PET studies were performed to investigate the kinetics and distribution of [18F]FSPG in naïve, control, pre-symptomatic, and symptomatic EAE mice, compared to 18F-fluorodeoxyglucose ([18F]FDG). After final PET scans, each mouse was perfused and radioactivity in dissected tissues was measured using a gamma counter. Central nervous system (CNS) tissues were further analyzed using ex vivo autoradiography or western blot. [18F]FSPG uptake in human monocytes, and T cells pre- and post-activation was investigated in vitro. RESULTS: [18F]FSPG was found to be more sensitive than [18F]FDG at detecting pathological changes in the spinal cord and brain of EAE mice. Even before clinical signs of disease, a small but significant increase in [18F]FSPG signal was observed in the spinal cord of EAE mice compared to controls. This increase in PET signal became more pronounced in symptomatic EAE mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise, in the brain of symptomatic EAE mice, [18F]FSPG uptake was significantly higher than controls, with the largest changes observed in the cerebellum. Western blot analyses of CNS tissues revealed a significant correlation between light chain of xc- (xCT) protein levels, the subunit of xc- credited with its transporter activity, and [18F]FSPG-PET signal. In vitro [18F]FSPG uptake studies suggest that both activated monocytes and T cells contribute to the observed in vivo PET signal. CONCLUSION: These data highlight the promise of [18F]FSPG-PET as a technique to provide insights into neuroimmune interactions in MS and the in vivo role of xc- in the development and progression of this disease, thus warranting further investigation.


Assuntos
Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Encefalomielite Autoimune Experimental/diagnóstico por imagem , Encefalomielite Autoimune Experimental/metabolismo , Radioisótopos de Flúor/metabolismo , Glutamatos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Animais , Células Cultivadas , Fluordesoxiglucose F18/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/metabolismo
5.
Muscle Nerve ; 57(3): 494-498, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29211916

RESUMO

INTRODUCTION: Evaluation of the nerve fascicular structure can be useful in diagnosing nerve damage, but it is a very challenging task with 3T MRI because of limited resolution. In this pilot study, we present the feasibility of high-resolution 7T MRI for examining the nerve fascicular structure. METHODS: A 3-dimensional (3D) gradient-spoiled sequence was used for imaging peripheral nerves in extremities. Images acquired with different in-plane resolutions (0.42 × 0.42 mm vs. 0.12 × 0.12 mm), and different main field strengths (7T vs. 3T) were compared. RESULTS: The individual nerve fascicles were identified at 0.12 × 0.12 mm resolution in both field strengths but not at 0.42 × 0.42 mm resolution. The fascicular structure was more sharply depicted in 7T images than in 3T images. DISCUSSION: High-resolution 3D imaging with 7T MRI demonstrated feasibility for imaging nerve fascicular structures. Muscle Nerve 57: 494-498, 2018.


Assuntos
Imagem por Ressonância Magnética/métodos , Nervos Periféricos/diagnóstico por imagem , Nervo Tibial/diagnóstico por imagem , Estudos de Viabilidade , Humanos , Imageamento Tridimensional , Projetos Piloto
6.
J Nucl Med ; 59(6): 967-972, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29097408

RESUMO

Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the causative pathology remains challenging. In this report, the feasibility of an 18F-FDG PET/MRI approach for improved diagnosis of chronic sciatica is presented. Methods:18F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers (healthy controls). Region-of-interest analysis using SUVmax was performed, and 18F-FDG uptake in lesions was compared with that in the corresponding areas in healthy controls. Results: Significantly increased 18F-FDG uptake was observed in detected lesions in all patients and was correlated with pain symptoms. 18F-FDG-avid lesions not only were found in impinged spinal nerves but also were associated with nonspinal causes of pain, such as facet joint degeneration, pars defect, or presumed scar neuroma. Conclusion: The feasibility of 18F-FDG PET/MRI for diagnosing pain generators in chronic sciatica was demonstrated, revealing various possible etiologies.


Assuntos
Fluordesoxiglucose F18 , Imagem por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Ciática/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/complicações , Ciática/complicações , Adulto Jovem
7.
Theranostics ; 7(11): 2794-2805, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824716

RESUMO

The ability to locate nerve injury and ensuing neuroinflammation would have tremendous clinical value for improving both the diagnosis and subsequent management of patients suffering from pain, weakness, and other neurologic phenomena associated with peripheral nerve injury. Although several non-invasive techniques exist for assessing the clinical manifestations and morphological aspects of nerve injury, they often fail to provide accurate diagnoses due to limited specificity and/or sensitivity. Herein, we describe a new imaging strategy for visualizing a molecular biomarker of nerve injury/neuroinflammation, i.e., the sigma-1 receptor (S1R), in a rat model of nerve injury and neuropathic pain. The two-fold higher increase of S1Rs was shown in the injured compared to the uninjured nerve by Western blotting analyses. With our novel S1R-selective radioligand, [18F]FTC-146 (6-(3-[18F]fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one), and positron emission tomography-magnetic resonance imaging (PET/MRI), we could accurately locate the site of nerve injury created in the rat model. We verified the accuracy of this technique by ex vivo autoradiography and immunostaining, which demonstrated a strong correlation between accumulation of [18F]FTC-146 and S1R staining. Finally, pain relief could also be achieved by blocking S1Rs in the neuroma with local administration of non-radioactive [19F]FTC-146. In summary, [18F]FTC-146 S1R PET/MR imaging has the potential to impact how we diagnose, manage and treat patients with nerve injury, and thus warrants further investigation.


Assuntos
Imagem por Ressonância Magnética/métodos , Neuralgia/diagnóstico por imagem , Neuralgia/patologia , Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/patologia , Tomografia por Emissão de Pósitrons/métodos , Receptores sigma/análise , Animais , Azepinas/administração & dosagem , Benzotiazóis/administração & dosagem , Modelos Animais de Doenças , Radioisótopos de Flúor/administração & dosagem , Marcação por Isótopo , Masculino , Neuroma/complicações , Ratos Sprague-Dawley
8.
Scand J Pain ; 15: 53-57, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28850345

RESUMO

BACKGROUND: Over the past couple of decades, a number of centers in the brain have been identified as important sites of nociceptive processing and are collectively known as the 'pain matrix.' Imaging tools such as functional magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) have played roles in defining these pain-relevant, physiologically active brain regions. Similarly, certain segments of the spinal cord are likely more metabolically active in the setting of pain conditions, the location of which is dependent upon location of symptoms. However, little is known about the physiologic changes in the spinal cord in the context of pain. This study aimed to determine whether uptake of 18F-FDG in the spinal cord on positron emission tomography/computed tomography (PET/CT) of patients with low back pain (LBP) differs from that of patients without LBP. METHODS: We conducted a retrospective review of 18F-FDG PET/CT scans of 26 patients with non-central nervous system cancers, 13 of whom had reported LBP and 13 of whom were free of LBP (controls). No patients had spinal stenosis or significant 18F-FDG contribution of degenerative changes of the spine into the spinal canal. Circular regions of interests were drawn within the spinal canal on transaxial images, excluding bony or discal elements of the spine, and the maximum standardized uptake value (SUVmax) of every slice from spinal nerves C1 to S1 was obtained. SUVmax were normalized by subtracting the SUVmax of spinal nerve L5, as minimal neural tissue is present at this level. Normalized SUVmax of LBP patients were compared to those of LBP-free patients at each vertebral level. RESULTS: We found the normalized SUVmax of patients with LBP to be significantly greater than those of control patients when jointly tested at spinal nerves of T7, T8, T9 and T10 (p<0.001). No significant difference was found between the two groups at other levels of the spinal cord. Within the two groups, normalized SUVmax generally decreased cephalocaudally. CONCLUSIONS: Patients with LBP show increased uptake of 18F-FDG in the caudal aspect of the thoracic spinal cord, compared to patients without LBP. IMPLICATIONS: This paper demonstrates the potential of 18F-FDG PET/CT as a biomarker of increased metabolic activity in the spinal cord related to LBP. As such, it could potentially aid in the treatment of LBP by localizing physiologically active spinal cord regions and guiding minimally invasive delivery of analgesics or stimulators to relevant levels of the spinal cord.


Assuntos
Dor Lombar/diagnóstico por imagem , Dor Lombar/metabolismo , Dor Nociceptiva/diagnóstico por imagem , Dor Nociceptiva/metabolismo , Medula Espinal/diagnóstico por imagem , Medula Espinal/metabolismo , Adulto , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Nervos Espinhais/diagnóstico por imagem , Nervos Espinhais/metabolismo
9.
J Nucl Med ; 58(12): 2004-2009, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28572487

RESUMO

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent 18F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one (18F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to 18F-FTC-146 were reported. High accumulation of 18F-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of 18F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade 18F-FTC-146 were successful. Injection of 18F-FTC-146 is safe, and absorbed doses are acceptable. The potential of 18F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.


Assuntos
Azepinas/farmacocinética , Benzotiazóis/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Azepinas/efeitos adversos , Azepinas/síntese química , Benzotiazóis/efeitos adversos , Benzotiazóis/síntese química , Feminino , Voluntários Saudáveis , Humanos , Marcação por Isótopo , Imagem por Ressonância Magnética , Masculino , Imagem Multimodal , Radiometria , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/síntese química , Receptores sigma/efeitos dos fármacos , Receptores sigma/metabolismo , Distribuição Tecidual , Imagem Corporal Total
10.
Mol Imaging Biol ; 19(5): 779-786, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28280965

RESUMO

PURPOSE: Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [18F]FTC-146, demonstrated high affinity for the S1R (K i = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; K i = 364 nM) across several species (from mouse to non-human primate). Herein, we report the clinical-grade radiochemistry filed with exploratory Investigational New Drug (eIND) and first-in-human PET/MRI evaluation of [18F]FTC-146. PROCEDURES: [18F]FTC-146 is prepared via a direct [18F] fluoride nucleophilic radiolabeling reaction and formulated in 0.9 % NaCl containing no more than 10 % ethanol through sterile filtration. Quality control (QC) was performed based on USP 823 before doses were released for clinical use. The safety and whole body biodistribution of [18F]FTC-146 were evaluated using a simultaneous PET/MR scanner in two representative healthy human subjects. RESULTS: [18F]FTC-146 was synthesized with a radiochemical yield of 3.3 ± 0.7 % and specific radioactivity of 8.3 ± 3.3 Ci/µmol (n = 10, decay corrected to EOB). Both radiochemical and chemical purities were >95 %; the prepared doses were stable for 4 h at ambient temperature. All QC test results met specified clinical criteria. The in vivo PET/MRI investigations showed that [18F]FTC-146 rapidly crossed the blood brain barrier and accumulated in S1R-rich regions of the brain. There were also radioactivity distributed in the peripheral organs, i.e., the lungs, spleen, pancreas, and thyroid. Furthermore, insignificant uptake of [18F]FTC-146 was observed in cortical bone and muscle. CONCLUSION: A reliable and automated radiosynthesis for providing routine clinical-grade [18F]FTC-146 for human studies was established in a modified GE TRACERlab FXFN. PET/MRI demonstrated the initial tracer biodistribution in humans, and clinical studies investigating different S1R-related diseases are in progress.


Assuntos
Azepinas/química , Azepinas/síntese química , Benzotiazóis/química , Benzotiazóis/síntese química , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Adulto , Azepinas/farmacocinética , Benzotiazóis/farmacocinética , Feminino , Humanos , Masculino , Distribuição Tecidual
11.
Sci Rep ; 5: 16342, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26552835

RESUMO

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (-89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (-81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner.


Assuntos
Terapia por Estimulação Elétrica , Dor de Ombro/terapia , Estimulação Elétrica Nervosa Transcutânea , Adulto , Animais , Dor Crônica , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Seguimentos , Humanos , Hiperalgesia/terapia , Hiperalgesia/veterinária , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Qualidade de Vida , Ratos , Resultado do Tratamento
12.
Clin Nucl Med ; 40(9): 720-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26053718

RESUMO

PURPOSE: The combined administration of F-NaF and F-FDG in a single PET/CT scan has the potential to improve patient convenience and cancer detection. Here we report the use of this approach for patients with sarcomas. PATIENTS AND METHODS: This is a retrospective review of 21 patients (12 men, 9 women; age, 19-66 years) with biopsy-proven sarcomas who had separate F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT scans for evaluation of malignancy. Two board-certified nuclear medicine physicians and 1 board-certified musculoskeletal radiologist were randomly assigned to review the scans. Results were analyzed for sensitivity and specificity, using linear regression and receiver operating characteristics. RESULTS: A total of 13 patients had metastatic disease on F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT. Skeletal disease was more extensive on the F-NaF PET/CT scan than on the F-FDG PET/CT in 3 patients, whereas in 1 patient, F-FDG PET/CT showed skeletal disease and the F-NaF PET/CT was negative. Extraskeletal lesions were detected on both F-FDG and combined F-NaF/F-FDG PET/CT in 20 patients, with 1 discordant finding in the lung. CONCLUSIONS: The combined F-NaF/F-FDG PET/CT scan allows for accurate evaluation of sarcoma patients. Further evaluation of this proposed imaging modality is warranted to identify the most suitable clinical scenarios, including initial treatment strategy and evaluation of response to therapy.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Sarcoma/diagnóstico por imagem , Fluoreto de Sódio/administração & dosagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Metástase Neoplásica , Sarcoma/patologia
13.
Yonsei Med J ; 56(4): 1106-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26069136

RESUMO

PURPOSE: Although the applications of adipose tissue-derived cells (ADCs) in regenerative medicine have been investigated, the role of ADCs in fracture healing remains unclear. In this study, we examined the fracture-healing effects and survival of transplanted ADCs using micro-computed tomography (CT) and bioluminescence imaging (BLI). MATERIALS AND METHODS: Luciferase-expressing ADCs were suspended in solubilized basement membrane preparation (SBMP) and xenografted on defects in the right femur of nude mice (n=5). SBMP alone was grafted on a defect in the contralateral femur. Serial in vivo micro-CT and BLI were performed for 20 days. Ex vivo BLI images of both femurs were obtained. Differences in the Hounsfield unit (HU), HU(ratio), and luciferase activities were compared using Wilcoxon signed-rank tests and non-parametric longitudinal analyses (p<0.05). RESULTS: In vivo BLI revealed a signal drop on day 2, reconstitution on day 5, and continuous decrement thereafter. Ex vivo BLI revealed residual activity in the ADC-implanted and adjacent areas. No activity was detected in the contralateral femur. The overall increment rate of normalized HUs was higher for ADC-treated femurs than for SBMP-treated femurs. Cell migration to distant injury sites was not detected. CONCLUSION: Enhanced bone density in the implant area suggests that ADCs have fracture-healing effects.


Assuntos
Tecido Adiposo/transplante , Consolidação da Fratura , Animais , Movimento Celular , Células Cultivadas , Fêmur , Camundongos , Camundongos Nus , Tomografia Computadorizada por Raios X , Microtomografia por Raio-X
14.
Semin Musculoskelet Radiol ; 19(2): 103-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25764234

RESUMO

Molecular and cellular imaging of neuropathic pain, utilizing the myriad of receptors and inflammatory mediators involved in nociceptive activity, is a promising approach toward objectively identifying peripheral pain generators. Neuropathic conditions arise from injured and inflamed nerves, which have been shown to elaborate several molecular and cellular elements that give rise to the neuropathic phenotype and can be exploited for imaging purposes. As such, in vivo approaches to image neuropathic pain mechanisms include imaging voltage-gated sodium channels with radiolabeled saxitoxin, calcium signaling with manganese-enhanced magnetic resonance imaging, and inflammatory changes and nerve metabolism with (18)F-fluorodeoxyglucose. Imaging approaches exploiting other mediators of nociceptive activity, such as substance P (neurokinin-1) receptor, sigma-1 receptor, and macrophages, have shown promising early advances in animal models. By combining the sensitivity and specificity of molecular imaging with the high anatomical, spatial and contrast resolution afforded by computed tomography and MRI, radiologists can potentially identify sites of nerve injury or neuroinflammation that are implicated as peripheral pain drivers with greater accuracy and confidence. In addition to guiding therapy, these approaches will aid in new drug designs for analgesia and more individualized treatment options.


Assuntos
Imagem por Ressonância Magnética/métodos , Neuralgia/diagnóstico , Neuralgia/fisiopatologia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Meios de Contraste , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Mediadores da Inflamação/análise , Canais Iônicos/metabolismo
15.
Oncol Rep ; 33(3): 1381-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25572125

RESUMO

There are conflicting data describing the effect of mesenchymal stem cells (MSCs) on tumorigenesis. The present study aimed to determine the survival rate and effect of adipose tissue-derived MSCs (ADMSCs) in tumor growth using bioluminescence imaging (BLI) and ultrasound (US) in an osteosarcoma xenograft model. Firefly luciferase-expressing ADMSCs combined with the osteosarcoma cell line UMR-106 in 4 different proportions (5, 10, 15 and 25%, named G1-G4, respectively) were xenografted into the right flanks of nude mice. The same number of UMR-106 cells was inoculated into the contralateral side of each mouse. Serial bioluminescence images were captured over 16 days to monitor the presence of ADMSCs in each group of 5 animals. The tumor volume was measured by ultra-high resolution US, and the tumor volume ratio (AMDSC mixed xenograft/control xenograft) was obtained to evaluate the effect of AMDSCs on tumor growth. Immunohistochemistry was performed to confirm the distribution of residual AMDSCs in the tumor. In G1, G2 and G3, the suppression of tumor growth by AMDSCs was noted in 2/5, 4/5 and 4/5 mice, respectively. However, accelerated tumor growth was noted in G4, which had the highest proportion of ADMSCs. The tumor volume ratio was significantly lower in G2 and G3 compared to G4, by Mann-Whitney U test (P=0.0159). Bioluminescence images demonstrated a serial decrement of the reporter gene for ADMSCs in the tumor mass without evidence of proliferation. Immunohistochemistry staining revealed minimal residual ADMSCs in the tumor periphery. Taken together, our data revealed that direct inoculation of ADMSCs into a tumor xenograft caused the death of the majority of ADMSCs in the tumor mass. Furthermore, relatively low proportions of ADMSCs suppressed the growth of osteosarcoma, while higher proportions showed a tumor-promoting effect.


Assuntos
Neoplasias Ósseas/terapia , Transformação Celular Neoplásica/patologia , Terapia Baseada em Transplante de Células e Tecidos , Transplante de Células-Tronco Mesenquimais , Osteossarcoma/terapia , Tecido Adiposo/citologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células-Tronco Mesenquimais , Camundongos , Camundongos Nus , Camundongos Transgênicos , Transplante de Neoplasias , Ratos , Transplante Heterólogo , Carga Tumoral
17.
J Am Coll Radiol ; 11(11): 1074-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25156201

RESUMO

PURPOSE: To investigate the prevalence of repetitive strain injury (RSI) among breast-imaging radiologists, the factors associated with such symptoms, and strategies to reduce injury. METHODS: In 2012, an anonymous survey regarding RSI and work habits was administered to 2,618 physician members of the Society of Breast Imaging via e-mail. Analysis of 727 (27.8%) de-identified responses was completed using STATA 12.1. Pain levels before and after implementation of digital imaging were compared with the Wilcoxon signed-rank test. The associations between RSI symptoms and work habits were assessed with logistic regression and test for trend. RESULTS: In the survey 438 of 727 (60.2%) respondents reported RSI symptoms, and 242 of 727 (33.3%) reported prior diagnosis/treatment. Results showed a statistically significant trend for the odds of RSI symptoms to increase with decreasing age (P = .0004) or increasing number of daily hours spent working (P = .0006), especially in an awkward position (P < .0001). Respondents recalled a significant increase in pain level after implementation of PACS, and a decrease in pain after ergonomic training or initiating use of an ergonomic mouse, adjustable chair, or adjustable table (P < .001, all comparisons). Only 17.7% (129 of 727) used an ergonomic mouse and 13.3% (97 of 727) had attended ergonomic training. Those with RSI symptoms or prior diagnosis of a Repetitive Strain Syndrome (RSS) were more likely to desire future ergonomic training compared with those without symptoms or injury (odds ratio 5.36, P < .001; odds ratio 2.63, P = .001, respectively). CONCLUSIONS: RSI is highly prevalent among breast-imaging radiologists nationwide and may worsen after implementation of PACS or with longer work hours. Ergonomic training and ergonomic devices may diminish or prevent painful RSI among radiologists.


Assuntos
Transtornos Traumáticos Cumulativos/etiologia , Transtornos Traumáticos Cumulativos/prevenção & controle , Mamografia , Traumatismos Ocupacionais/etiologia , Traumatismos Ocupacionais/prevenção & controle , Entorses e Distensões/etiologia , Entorses e Distensões/prevenção & controle , Adulto , Idoso , Estudos Transversais , Transtornos Traumáticos Cumulativos/epidemiologia , Ergonomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Entorses e Distensões/epidemiologia , Inquéritos e Questionários
18.
J Nucl Med ; 55(1): 147-53, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24337599

RESUMO

UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation. METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum. RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents. CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.


Assuntos
Azepinas/química , Benzotiazóis/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Receptores sigma/química , Animais , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão , Humanos , Ligantes , Imagem por Ressonância Magnética , Masculino , Camundongos , Microssomos Hepáticos/metabolismo , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Saimiri , Distribuição Tecidual , Tomografia Computadorizada por Raios X
19.
J Am Chem Soc ; 135(48): 18012-5, 2013 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-24261833

RESUMO

Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent, NaV-selective inhibitor saxitoxin. Both autoradiography analysis of sciatic nerves excised from injured rats as well as whole animal PET-MR imaging demonstrate that a systemically administered [(18)F]-labeled saxitoxin derivative concentrates at the site of nerve injury, consistent with upregulated sodium channel expression following axotomy. This type of PET agent has potential use for serial monitoring of channel expression levels at injured nerves throughout wound healing and/or following drug treatment. Such information may be correlated with pain behavioral analyses to help shed light on the complex molecular processes that underlie pain sensation.


Assuntos
Neuralgia/diagnóstico , Saxitoxina/análogos & derivados , Nervo Isquiático/lesões , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Canais de Sódio Disparados por Voltagem/análise , Animais , Radioisótopos de Flúor/química , Imagem por Ressonância Magnética , Neuralgia/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Saxitoxina/síntese química , Nervo Isquiático/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química , Canais de Sódio Disparados por Voltagem/metabolismo
20.
AJR Am J Roentgenol ; 201(2): 264-77, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23795682

RESUMO

OBJECTIVE: A review of the innovative role molecular imaging plays in musculoskeletal radiology is provided. Musculoskeletal molecular imaging is under development in four key areas: imaging the activity of osteoblasts and osteoclasts, imaging of molecular and cellular biomarkers of arthritic joint destruction, cellular imaging of osteomyelitis, and imaging generators of musculoskeletal pain. CONCLUSION: Together, these applications suggest that next-generation musculoskeletal radiology will facilitate quantitative visualization of molecular and cellular biomarkers, an advancement that appeared futuristic just a decade ago.


Assuntos
Imagem Molecular/tendências , Doenças Musculoesqueléticas/diagnóstico , Biomarcadores , Difusão de Inovações , Humanos
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