RESUMO
We report a case of 2 sisters in their 20s with genetically confirmed UDP-N-acetylglucoasmine 2-epimerase/N-acetylmannosamine kinase myopathy along with muscle biopsy findings. Both patients described slowly progressive signs of distal-predominant weakness since adolescence that had been dismissed as "clumsiness." Exam and electrodiagnostic testing suggested a predominately distal myopathy. Muscle biopsy of the left tibialis anterior revealed rimmed vacuoles and, interestingly, also had characteristic features of a myofibrillar myopathy. Genetic testing confirmed a diagnosis of autosomal recessive GNE myopathy in both patients. GNE myopathy has not typically been considered a myofibrillar myopathy, but this case raises possibilities worthy of further exploration. It is possible that the unique combination of pathogenic alleles in GNE reported here has led to a novel form of GNE myopathy with muscle biopsy showing characteristic features of GNE myopathy and myofibrillar myopathy. The other possibility is that myofibrillar myopathy may be a more common feature of GNE myopathies than classically described.
Assuntos
Miopatias Distais/diagnóstico , Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/diagnóstico , Adulto , Biópsia , Feminino , Humanos , MutaçãoRESUMO
Primary melanocytic disease of the central nervous system is a rarely encountered condition currently without consensus on treatment and lacking major guidelines for management. Understanding the nature of the disease and differentiating primary melanocytic disease from the much more commonly encountered secondary (metastatic) melanoma is important in identifying the condition and pursuing appropriate treatment.
Assuntos
Melanócitos/patologia , Melanoma/patologia , Carcinomatose Meníngea/patologia , Idoso , Carcinoma Papilar/patologia , Feminino , Humanos , Segunda Neoplasia Primária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated. Four of five of the patients had potential clinical benefit (partial response or stable disease greater than 6 months on therapy). We further describe the specific drug properties of each agent chosen and discuss characteristics relevant in their evaluation for therapeutic suitability. Finally, we summarize both tumor and drug characteristics that impact the ability to successfully incorporate targeted therapies into CNS malignancy management.
Assuntos
Antineoplásicos/uso terapêutico , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Medicina de Precisão/métodos , Antineoplásicos/farmacocinética , Criança , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Seleção de Pacientes , Valor Preditivo dos TestesRESUMO
Pediatric spinal oligodendrogliomas are rare and aggressive tumors. They do not share the same molecular features of adult oligodendroglioma, and no previous reports have examined the molecular features of pediatric spinal oligodendroglioma. We present the case of a child with a recurrent spinal anaplastic oligodendroglioma. We performed whole exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which revealed somatic mutations in NF1 and FGFR1. These data allowed us to explore potential personalized therapies for this patient and expose molecular drivers that may be involved in similar cases.
Assuntos
Deleção de Genes , Proteínas de Neoplasias , Neurofibromina 1 , Oligodendroglioma , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Neoplasias da Coluna Vertebral , Pré-Escolar , Exoma , Feminino , Humanos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neurofibromina 1/biossíntese , Neurofibromina 1/genética , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/biossíntese , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/metabolismo , TranscriptomaRESUMO
Nocardia species are an infrequent cause of brain abscesses. We report a 50-year-old man with Nocardia paucivorans cerebral abscesses. Brain MRI revealed innumerable small ring-enhancing lesions. The patient initially responded to treatment with antibiotics and steroids, but experienced worsening after discontinuation of steroids. Brain biopsy performed to exclude central nervous system lymphoma produced nodular tissue with branching filaments on silver stain. Steroids were re-initiated and tapered slowly. The patient completed 1year of antibiotic therapy, after which he had no neurological symptoms and complete resolution of all brain abscesses on MRI.
Assuntos
Abscesso Encefálico/tratamento farmacológico , Nocardiose/tratamento farmacológico , Nocardia , Antibacterianos/uso terapêutico , Abscesso Encefálico/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Nocardiose/patologia , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Delayed swelling after skull fractures is an uncommon complication following head trauma in children. Classically, growing skull fractures typically present in patients under 3 years of age with progressive subcutaneous fluid collections, or occasionally with neurologic symptoms. We present the case of a healthy 2-year-old boy with a lytic "punched-out" frontal skull lesion. The child presented 2 months after a minor forehead injury for which no medical attention was sought. METHODS: The skull defect had no associated leptomeningeal cyst or brain herniation. Imaging and presentation were thought to be consistent with eosinophilic granuloma. Histologic findings demonstrated a healing skull fracture. RESULTS: Cranioplasty was performed, and the patient had an uncomplicated postoperative course. CONCLUSIONS: In this report, we describe our experience with this atypical presentation of a healing skull fracture mimicking a typical eosinophilic granuloma.
Assuntos
Craniotomia , Granuloma Eosinófilo/fisiopatologia , Fraturas Cranianas/cirurgia , Pré-Escolar , Humanos , Imageamento Tridimensional , Masculino , Tomógrafos ComputadorizadosRESUMO
Malignant peripheral nerve sheath tumors (MPNSTs) are rare, affecting only a small portion of the general population. In many cases, MPNSTs occur in association with neurofibromatosis Type 1 and at times arise secondary to previous radiation therapy (RT). These tumors can be found essentially anywhere a peripheral nerve is present, but they rarely originate primarily from the spinal nerve or cauda equina and cause leptomeningeal spread. This report describes the treatment course of a 43-year-old man with a history of testicular seminoma treated with RT a decade before, who was found to have a large sacral MPNST. The patient underwent complete sacrectomy for gross-total resection. Despite this effort, he was eventually found to have metastatic lesions throughout the spine and brain, ultimately resulting in acute hydrocephalus and death. Biopsy results of these metastatic lesions proved to be characteristic of his original MPNST. The literature is also reviewed and the diagnostic modalities, management strategies, and prognosis of MPNST are discussed.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Cauda Equina/efeitos da radiação , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/cirurgia , Neoplasias Induzidas por Radiação/terapia , Neoplasias de Bainha Neural/etiologia , Adulto , Biópsia , Terapia Combinada , Meios de Contraste , Crioterapia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Embrionárias de Células Germinativas/radioterapia , Neoplasias Induzidas por Radiação/patologia , Neoplasias de Bainha Neural/patologia , Neoplasias de Bainha Neural/terapia , Procedimentos Neurocirúrgicos , Sacro , Neoplasias Testiculares/radioterapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND CONTEXT: Human recombinant bone morphogenetic protein-2 (BMP-2) is commonly used in spinal surgery to augment arthrodesis, and a number of potential complications have been documented. PURPOSE: To present the case of a delayed radiculopathy that occurred because of a calcified perineural cyst that formed after an L4-L5 transforaminal lumbar interbody fusion (TLIF) in which BMP-2 was used. STUDY DESIGN/SETTING: Case report of a 70-year-old man presented with back and right lower extremity pain. METHODS: A 70-year-old man who had previously undergone a right L4-L5 TLIF presented 20 months after surgery with progressively radiating right leg pain. Imaging revealed a right-sided L4-L5 cystic lesion posterior to the interbody cage. The patient underwent reexploration, and a calcified mass was discovered. RESULTS: Histopathology revealed fragments of organized collagenous connective tissue, new collagen, and partially calcified fragments of fibrocartilage, bone, and ligament. CONCLUSIONS: This is the first reported case of a symptomatic calcified perineural cyst developing after a fusion procedure in which BMP-2 was used. The presence of connective tissue with metaplastic bone formation and maturation within the lesion suggests that formation of the cyst was secondary to application of BMP-2, as it possesses both osteogenic and chondrogenic capabilities.
Assuntos
Proteínas Morfogenéticas Ósseas/efeitos adversos , Vértebras Lombares/cirurgia , Radiculopatia/etiologia , Fusão Vertebral/efeitos adversos , Cistos de Tarlov/etiologia , Idoso , Proteínas Morfogenéticas Ósseas/uso terapêutico , Humanos , Vértebras Lombares/patologia , Masculino , Radiculopatia/patologia , Radiculopatia/cirurgia , Fusão Vertebral/instrumentação , Cistos de Tarlov/patologia , Cistos de Tarlov/cirurgiaRESUMO
INTRODUCTION: We present a Jordanian man with the typical LGMD 2L phenotype of early, asymmetric quadriceps weakness and subsequent biceps brachii weakness. METHODS: Case report. RESULTS: Muscle biopsies document a progressive dystrophic pattern unrelated to known sarcolemmal defects associated with muscular dystrophy. Genetic testing revealed novel, heterozygote Anoctamin 5 gene mutations. CONCLUSIONS: This case report expands the known mutations resulting in LGMD 2L and supports the assertion that Anoctamin 5 mutations are more prevalent than previously recognized.
Assuntos
Canais de Cloreto/genética , Debilidade Muscular/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Adulto , Anoctaminas , Humanos , Masculino , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/patologia , MutaçãoRESUMO
Radiology provides valuable gross pathologic information about central nervous system (CNS) infections. Major categories of infectious lesions of the brain and spinal cord are recognized by imaging such as diffuse, focal, or multifocal. This article discusses the pathologic basis of these radiographic findings. It illustrates examples with gross and microscopic photographs of CNS infections, and the tissue reactions to these infections. Where the organism can spread within the CNS, and cellular responses to the organism underlie both the radiographic and pathologic findings.
Assuntos
Infecções do Sistema Nervoso Central/patologia , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Biópsia , Encéfalo/patologia , Encéfalo/cirurgia , Infecções do Sistema Nervoso Central/etiologia , Infecções do Sistema Nervoso Central/cirurgia , Comportamento Cooperativo , Diagnóstico Diferencial , Humanos , Comunicação Interdisciplinar , Medula Espinal/patologia , Medula Espinal/cirurgiaRESUMO
Three cases of different types of neuromuscular diseases demonstrate different muscle responses to external stress or intrinsic muscle abnormalities. The first muscle biopsy shows stenosis of its vessels causing acute muscle ischemia, stress from an external vascular disease. The muscle response is similar to the cellular necrosis seen in primary muscle diseases (myopathies), but the histologic pattern is more focal than most myopathies. The second muscle biopsy demonstrates the effects of external motor nerve injury or disease causing groups of muscle fibers to atrophy. If a nerve reinnervates the muscle, it changes the fiber types in distinct patterns. The third muscle biopsy shows an intrinsic muscle abnormality causes chronic failure of the muscle fibers to thrive and repeated attempts by the fibers to regenerate, stimulating other tissue repair processes, like fibrosis, to change the muscle. Depending on the etiologic factor, muscle will respond to internal and external influences in different manners.
Assuntos
Músculos/patologia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/patologia , Adulto , Criança , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Distrofia Muscular de Emery-Dreifuss/patologia , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Doenças Neuromusculares/etiologia , Doenças Neuromusculares/fisiopatologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Doenças Vasculares/diagnóstico , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologiaRESUMO
Tumor-initiating cells have been suggested to be rare in many cancers. We tested this in mouse malignant peripheral nerve sheath tumors (MPNSTs) and found that 18% of primary and 49% of passaged MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice formed tumors upon transplantation, whereas only 1.8% to 2.6% of MPNST cells from Nf1(+/-); p53(+/-) mice did. MPNST cells of both genotypes require laminin binding to ß1-integrin for clonogenic growth. Most MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice expressed laminin, whereas most MPNST cells from Nf1(+/-); p53(+/-) mice did not. Exogenous laminin increased the percentage of MPNST cells from Nf1(+/-); p53(+/-) but not Nf1(+/-); Ink4a/Arf(-/-) mice that formed tumorigenic colonies. Tumor-forming potential is common among MPNST cells, but the assay conditions required to detect it vary with tumor genotype.
Assuntos
Transformação Celular Neoplásica , Neoplasias de Bainha Neural/patologia , Animais , Proliferação de Células , Genótipo , Integrina beta1/metabolismo , Integrina beta1/fisiologia , Laminina/metabolismo , Camundongos , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/metabolismo , Células Tumorais CultivadasRESUMO
Infantile hemangiomas are tumors commonly seen in children. Few authors have reported infantile hemangiomas affecting the CNS, and there are no prior reports detailing spontaneous resolution of a histologically proven juvenile hemangioma within a dorsal root ganglion. The authors report the case of a newborn boy with a large cutaneous hemangioma in the midline of his back. Spinal MR images were obtained to rule out associated spinal cord tethering, and an intradural spinal lesion was unexpectedly discovered. Biopsy revealed an intradural infantile hemangioma within the dorsal root ganglion, and, based on this diagnosis, no resection was performed. Sixteen months following the biopsy, the cutaneous hemangioma had become involuted and the intradural hemangioma had completely resolved. The behavior of the intradural component in this case follows the natural history of many cutaneous infantile hemangiomas.
Assuntos
Gânglios Espinais/patologia , Hemangioma/diagnóstico , Pele/patologia , Humanos , Recém-Nascido , Masculino , Remissão EspontâneaRESUMO
BACKGROUND AND IMPORTANCE: Langerhans cell histiocytosis (LCH) is an uncommon disease, usually affecting the cranium and peripheral bones. We present a rare case of isolated optic chiasm involvement by LCH to highlight the importance of considering LCH in the differential diagnosis of optic chiasm lesions. CLINICAL PRESENTATION: A 71-year-old woman presented with a 6-week history of worsening peripheral vision, headaches, weakness, cold sensitivity, and fatigue. She was found to have dense bitemporal hemianopsia. Magnetic resonance imaging revealed a 2-cm lesion, contrast enhancing on T1 and bright on T2 signal, involving the optic chiasm but not the pituitary gland. Preoperative considerations included optic nerve glioma, choristoma of the stalk, sarcoid, hypothalamic glioma, and Langerhans cell histiocytosis. The patient underwent a right subfrontal craniotomy for biopsy of the lesion. The optic chiasm was grossly enlarged with no tissue external to the chiasm. A midline incision was made in the lamina terminalis, and multiple biopsies were taken of firm fibrous material. Histologically, the tumor was characteristic for LCH and included a mixture of histiocytes with features of Langerhans cells, eosinophils, small lymphocytes, macrophages, neutrophils, and plasma cells. CONCLUSION: LCH is a rare disease, generally affecting bone, skin, lymph nodes, and in more severe cases, visceral organs. LCH involving the optic pathways is a rare condition that should be included in the differential for adults with mass lesions involving the orbit, eye, optic nerve, or chiasm. Future clinical and basic science research is needed to better understand LCH, its molecular origin, and its growth pattern.
Assuntos
Histiocitose de Células de Langerhans/patologia , Quiasma Óptico/patologia , Neoplasias do Nervo Óptico/patologia , Idoso , Feminino , Histiocitose de Células de Langerhans/radioterapia , Histiocitose de Células de Langerhans/cirurgia , Humanos , Imuno-Histoquímica , Quiasma Óptico/cirurgia , Neoplasias do Nervo Óptico/cirurgiaRESUMO
Recent studies have identified genes and core pathways that are altered in human glioblastoma. However, the mechanisms by which alterations of these glioblastoma genes singly and cooperatively transform brain cells remain poorly understood. Further, the cell of origin of glioblastoma is largely elusive. By targeting a p53 in-frame deletion mutation to the brain, we show that p53 deficiency provides no significant growth advantage to adult brain cells, but appears to induce pleiotropic accumulation of cooperative oncogenic alterations driving gliomagenesis. Our data show that accumulation of a detectable level of mutant p53 proteins occurs first in neural stem cells in the subventricular zone (SVZ) and that subsequent expansion of mutant p53-expressing Olig2(+) transit-amplifying progenitor-like cells in the SVZ-associated areas initiates glioma formation.
Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Linhagem da Célula/fisiologia , Transformação Celular Neoplásica/metabolismo , Células-Tronco Multipotentes/patologia , Neurônios/patologia , Proteína Supressora de Tumor p53/biossíntese , Animais , Astrócitos/patologia , Astrócitos/fisiologia , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Diferenciação Celular , Transformação Celular Neoplásica/patologia , Corpo Caloso/metabolismo , Corpo Caloso/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Células-Tronco Multipotentes/fisiologia , Mutação , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1(fl/-) mice developed neurofibromas, and Nf1(+/-)Ink4a/Arf(-/-) and Nf1/p53(+/-) mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.
Assuntos
Neoplasias/patologia , Crista Neural/citologia , Neurofibromina 1/deficiência , Células-Tronco/citologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Mutação/genética , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Neoplasias de Bainha Neural/patologia , Crista Neural/efeitos dos fármacos , Neurofibroma Plexiforme/patologia , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/embriologia , Sistema Nervoso Periférico/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/patologia , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteínas ras/metabolismoRESUMO
A 5-year-old girl with progressive hemiparesis and headache was found by brain imaging to have a large tumor centered at the foramen of Monro, blocking cerebrospinal outflow and producing massive lateral ventriculomegaly. Total excision of the mass led to a pathologic diagnosis of giant cell astrocytoma. Dermatologic abnormalities had been detected shortly after birth but were unexplained. Abdominal imaging disclosed renal cysts, and ophthalmologic examination disclosed papilledema and retinal plaques. On this basis, a diagnosis of tuberous sclerosis (TS) was finally made. Two months after surgery, papilledema had resolved, and visual function appeared to be normal. Although the patient apparently escaped visual loss, other reports affirm that giant cell astrocytoma, a common tumor in TS, may go undetected for long enough to produce irreversible optic neuropathy from chronic papilledema. Because patients with TS may not report visual loss, they should undergo periodic ophthalmologic screening.
Assuntos
Astrocitoma/complicações , Neoplasias do Ventrículo Cerebral/complicações , Hidrocefalia/complicações , Papiledema/etiologia , Esclerose Tuberosa/complicações , Astrocitoma/diagnóstico , Astrocitoma/cirurgia , Neoplasias do Ventrículo Cerebral/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/cirurgia , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos/métodos , Papiledema/diagnóstico , Esclerose Tuberosa/diagnósticoRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to assess the use of diffusion tensor imaging (DTI) in the evaluation of new contrast-enhancing lesions and perilesional edema in patients previously treated for brain neoplasm in the differentiation of recurrent neoplasm from treatment-related injury. METHODS: Twenty-eight patients with new contrast-enhancing lesions and perilesional edema at the site of previously treated brain neoplasms were retrospectively reviewed. Nine directional echoplanar DTIs with b=1000 s/mm(2) were obtained using a single-shot spin-echo echoplanar imaging. Standardized regions of interest were manually drawn in several regions. Mean apparent diffusion coefficient (ADC), fractional anisotropy (FA) and eigenvalue indices (lambda( parallel) and lambda( perpendicular)) and their ratios relative to the contralateral side were compared in patients with recurrent neoplasm versus patients with radiation injury, as established by histological examination or by clinical course, including long-term imaging studies and magnetic resonance spectroscopy. RESULTS: The ADC values in the contrast-enhancing lesions were significantly higher (P=.01) for the recurrence group (range=1.01 x 10(-3) to 1.66 x 10(-3) mm(2)/s; mean+/-S.D.=1.27+/-0.15) than for the nonrecurrence group (range=0.9 x 10(-3) to 1.31 x 10(-3) mm(2)/s; mean+/-S.D.=1.12+/-0.14). The ADC ratios in the white matter tracts in perilesional edema trended higher (P=.09) in treatment-related injury than in recurrent neoplasm (mean+/-S.D.=1.85+/-0.30 vs. 1.60+/-0.27, respectively). FA ratios were significantly higher in normal-appearing white matter (NAWM) tracts adjacent to the edema in the nonrecurrence group (mean+/-S.D.=0.89+/-0.15) than in those in the recurrence group (mean+/-S.D.=0.74+/-0.14; P=.03). Both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in contrast-enhancing lesions in the recurrence group than in those in the nonrecurrence group (P=.02). As well, both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in perilesional edema than in normal white matter (P<.01 and P<.001, respectively) in both groups. CONCLUSION: The assessment of diffusion properties, especially ADC values and ADC ratios, in contrast-enhancing lesions, perilesional edema and NAWM adjacent to the edema in the follow-up of new contrast-enhancing lesions at the site of previously treated brain neoplasms may add to the information obtained by other imaging techniques in the differentiation of radiation injury from tumor recurrence.
Assuntos
Edema Encefálico/diagnóstico , Neoplasias Encefálicas/diagnóstico , Imagem de Difusão por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Lesões por Radiação/diagnóstico , Adolescente , Adulto , Edema Encefálico/patologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Meios de Contraste , Diagnóstico Diferencial , Imagem Ecoplanar , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Lesões por Radiação/patologia , Estudos RetrospectivosRESUMO
Functional diffusion map (fDM) has been recently reported as an early and quantitative biomarker of clinical brain tumor treatment outcome. This approach spatially maps and quantifies treatment-induced changes in tumor water diffusion values resulting from alterations in cell density/cell membrane function and microenvironment. This current study was designed to evaluate the capability of fDM for preclinical evaluation of dose escalation studies and to determine if these changes were correlated with outcome measures (cell kill and overall survival). Serial T2-weighted were carried out on rodents with orthotopically implanted 9L brain tumors receiving three doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (6.65, 13.3, and 26.6 mg/kg, i.p.). All images were coregistered to baseline T2-weighted images for fDM analysis. Analysis of tumor fDM data on day 4 posttreatment detected dose-dependent changes in tumor diffusion values, which were also found to be spatially dependent. Histologic analysis of treated tumors confirmed spatial changes in cellularity as observed by fDM. Early changes in tumor diffusion values were found to be highly correlative with drug dose and independent biologic outcome measures (cell kill and survival). Therefore, The fDM imaging biomarker for early prediction of treatment efficacy can be used in the drug development process.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Antineoplásicos Alquilantes/farmacologia , Carmustina/farmacologia , Difusão , Relação Dose-Resposta a Droga , Imageamento por Ressonância Magnética/métodos , Masculino , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344 , Resultado do TratamentoRESUMO
We present a method for registering histology and in vivo imaging that requires minimal microtoming and is automatic following the user's initialization. In this demonstration, we register a single hematoxylin-and-eosin-stained histological slide of a coronal section of a rat brain harboring a 9L gliosarcoma with an in vivo 7T MR image volume of the same brain. Because the spatial resolution of the in vivo MRI is limited, we add the step of obtaining a high spatial resolution, ex vivo MRI in situ for intermediate registration. The approach taken was to maximize mutual information in order to optimize the registration between all pairings of image data whether the sources are MRI, tissue block photograph, or stained sample photograph. The warping interpolant used was thin plate splines with the appropriate basis function for either 2-D or 3-D applications. All registrations were implemented by user initialization of the approximate pose between the two data sets, followed by automatic optimization based on maximizing mutual information. Only the higher quality anatomical images were used in the registration process; however, the spatial transformation was directly applied to a quantitative diffusion image. Quantitative diffusion maps from the registered location appeared highly correlated with the H&E slide. Overall, this approach provides a robust method for coregistration of in vivo images with histological sections and will have broad applications in the field of functional and molecular imaging.