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A variety of Magnetic Resonance (MR) and nuclear medicine (NM) techniques have been used in symptomatic and presymptomatic SCA2 gene carriers to explore,in vivo, the physiopathological biomarkers of the neurological dysfunctions characterizing the associated progressive disease that presents with a cerebellar syndrome, or less frequently, with a levodopa-responsive parkinsonian syndrome. Morphometry performed on T1-weighted images and diffusion MR imaging enable structural and microstructural evaluation of the brain in presymptomatic and symptomatic SCA2 gene carriers, in whom they show the typical pattern of olivopontocerebellar atrophy observed at neuropathological examination. Proton MR spectroscopy reveals, in the pons and cerebellum of SCA2 gene carriers,a more pronounced degree of abnormal neurochemical profile compared to other spinocerebellar ataxias with decreased NAA/Cr and Cho/Cr, increased mi/Cr ratios, and decreased NAA and increased mI concentrations. These neurochemical abnormalities are detectable also in presymtomatic gene carriers. Resting state functional MRI (rsfMRI) demonstrates decreased functional connectivity within the cerebellum and of the cerebellum with fronto-parietal cortices and basal ganglia in symptomatic SCA2 subjects. 18F-fluorodeoxyglucose Positron Emission Tomography (PET) shows a symmetric decrease of the glucose uptake in the cerebellar cortex, the dentate nucleus, the brainstem and the parahippocampal cortex. Single photon emission tomography and PET using several radiotracers have revealed almost symmetric nigrostriatal dopaminergic dysfunction irrespective of clinical signs of parkinsonism which are already present in presymtomatic gene carriers. Longitudinal small size studies have proven that morphometry and diffusion MR imaging can track neurodegeneration in SCA2, and hence serve as progression biomarkers. So far, such a capability has not been reported for proton MR spectroscopy, rsfMRI and NM techniques. A search for the best surrogate marker for future clinical trials represents the current challenge for the neuroimaging community.
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Ataxina-2/genética , Ataxina-2/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Neuroimagen/métodos , Encéfalo/metabolismo , Encéfalo/patología , Progresión de la Enfermedad , Heterocigoto , Humanos , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/patologíaRESUMEN
Oculomeningovascular amyloidosis is a variant of transthyretin (TTR) amyloidotic polyneuropathy, which is associated with blindness and brain ischemia, microhemorrages, and siderosis due to prominent production of the abnormal TTR in the eye and in the choroid plexuses. Tafamidis is a TTR stabilizer that is orally administered and, by interfering with amyloid fibril formation and deposition, is capable of slowing progression of TTR polyneuropathy and of early-stage cardiomyopathy. However, the ocular manifestations of amyloid deposition progressed despite tafamidis therapy in Val30Met TTR amyloidosis, and the effects of tafamidis on meningovascular amyloidosis are unknown. We observed failure of tafamidis to halt progression of oculomeningovascular amyloid deposition in a patient with familial Ala36Pro TTR amyloidosis. She received molecular diagnosis at age 24 and presented at age 26 with paresthesias of the lower limbs and bowel dysfunction. Echography showed minimal amyloid opacities in the corpus vitreum. Treatment with tafamidis meglumine was started. Sixteen months later, she complained of severe headache followed by left hemiparesthesias and numbness lasting 20 minutes. Magnetic resonance imaging showed multiple focal and diffuse hemosiderin deposits compatible with microbleeds and early siderosis. Echography showed a marked increase of "vitreal opacities." Our observation confirms that tafamidis fails in halting increase of vitreal amyloid deposits and indicates that it is presumably ineffective in preventing clinical onset due to progression of meningovascular amyloidosis. These failures may be due to the incapability of tafamidis to cross the blood-retina and blood-brain barriers. Therapeutic options targeting oculomeningovascular TTR amyloidoses in humans are required.
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Neuropatías Amiloides Familiares/tratamiento farmacológico , Benzoxazoles/uso terapéutico , Trastornos Cerebrovasculares/tratamiento farmacológico , Oftalmopatías/tratamiento farmacológico , Mutación , Prealbúmina/genética , Siderosis/tratamiento farmacológico , Adulto , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/genética , Ceguera/tratamiento farmacológico , Ceguera/genética , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genética , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/genética , Progresión de la Enfermedad , Oftalmopatías/diagnóstico , Oftalmopatías/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hemorragias Intracraneales/tratamiento farmacológico , Hemorragias Intracraneales/genética , Imagen por Resonancia Magnética , Fenotipo , Siderosis/diagnóstico , Siderosis/genética , Insuficiencia del Tratamiento , UltrasonografíaRESUMEN
Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon condition of unknown etiology occurring in children and adults. Pathological findings include obliterative hyalinosis of the small vessels, myelin loss, intense gliosis, Rosenthal fiber formation, microcalcifications, and hemosiderin deposits. Herein we report a 55-year-old man with LCC documented 10 years ago, in whom we examined brain perfusion by pseudocontinuous arterial spin labeling technique. We demonstrated diffused hypoperfusion of the affected white matter (WM) and of the subcortical gray matter (GM) and cortical GM in the patient in comparison to a group of healthy control subjects, using both qualitative evaluation and region of interest analysis. WM and subcortical GM hypoperfusion reflects the known distribution of LCC microangiopathy. We speculate that cortical hypoperfusion may be related to cerebral atrophy or may reflect deafferentation secondary to severe leukoencephalopathy, and may possibly contribute to severe motor and cognitive impairment. Further studies addressing cerebral blood flow in LCC are necessary.
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Isquemia Encefálica/etiología , Calcinosis/complicaciones , Quistes/complicaciones , Leucoencefalopatías/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Quistes/diagnóstico por imagen , Humanos , Leucoencefalopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.
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Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/patología , Animales , Enfermedades Cerebelosas/metabolismo , Cerebelo/metabolismo , Cerebelo/patología , Consenso , Humanos , Neuroimagen/métodosRESUMEN
OBJECTIVE: This study aimed to define computed tomographic morphologic features of lung cancer associated with cystic airspaces, their modifications in serial computed tomographic scans, and 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography uptake. METHODS: Computed tomographic scans and 18F-FDG positron emission tomography in 24 patients with lung cancer (17 adenocarcinomas, 7 squamous cell carcinomas, 12 stage I and 12 stage II to IV) associated with cystic airspaces were reviewed. RESULTS: Mean diameter of airspace was initially 17.6 mm (range, 5-30 mm), and 4 morphologic patterns were recognized: solid nodule protruding externally (type I, n = 5) or internally (type II, n = 4) from the cyst wall; circumferential thickening of the cyst wall (type III, n = 8); and tissue intermixed within clusters of cysts (type IV, n = 7). With tumor growth, airspace size decreased in 9, increased in 6, and was unchanged in 9 cases. Five cases evolved from type III to type I, and 5 lesions became completely solid. 18F-fluoro-2-deoxy-D-glucose uptake was initially absent to mild in 7 and moderate to marked in 14 lesions. CONCLUSIONS: Progressive wall thickening or appearance/increase of a nodule inside or outside a cystic airspace should raise suspicion of lung cancer irrespective of FDG uptake.
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Quistes/diagnóstico , Fluorodesoxiglucosa F18 , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Quistes/complicaciones , Quistes/metabolismo , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Aumento de la Imagen/métodos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Despite evidence of a cerebellar contribution to language, possible functional changes of the cerebellum in patients with language impairment secondary to cerebral neurodegeneration has not been investigated so far. We examined with resting perfusion single photon emission tomography one patient with semantic dementia and the data were compared with a normal subject database. Region of interest and Statistical Parametric Mapping 2 analysis showed in the patient hypoperfusion of the left temporal and parietal lobe and hyperperfusion in the superior vermis and cerebellar hemispheres (lobules IV, V, and VI). The cerebellum shows increased flow of possible compensatory significance in patients with language disturbance associated to cerebral degenerative changes.
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Afasia Progresiva Primaria/diagnóstico por imagen , Cerebelo/irrigación sanguínea , Demencia Frontotemporal/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/etiología , Cerebelo/diagnóstico por imagen , Femenino , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Magnetic resonance imaging (MRI and single-photon emission computed tomography (SPECT) have a considerable role in the diagnosis of the single patient with movement disorders. Conventional MRI demonstrates symptomatic causes of parkinsonism but does not show any specific finding in Parkinson's disease (PD). However, SPECT using tracers of the dopamine transporter (DAT) demonstrates an asymmetric decrease of the uptake in the putamen and caudate from the earliest clinical stages. In other degenerative forms of parkinsonism, including progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD), MRI reveals characteristic patterns of regional atrophy combined with signal changes or microstructural changes in the basal ganglia, pons, middle and superior cerebellar peduncles, and cerebral subcortical white matter. SPECT demonstrates a decreased uptake of tracers of the dopamine D2 receptors in the striata of patients with PSP and MSA, which is not observed in early PD. MRI also significantly contributes to the diagnosis of some inherited hyperkinetic conditions including neurodegeneration with brain iron accumulation and fragile-X tremor/ataxia syndrome by revealing characteristic symmetric signal changes in the basal ganglia and middle cerebellar peduncles, respectively. A combination of the clinical features with MRI and SPECT is recommended for optimization of the diagnostic algorithm in movement disorders.
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Imagen por Resonancia Magnética/métodos , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/diagnóstico , Tomografía Computarizada de Emisión de Fotón Único/métodos , Algoritmos , Humanos , Interpretación de Imagen Asistida por Computador , Trastornos del Movimiento/etiología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The lack of visualization of the spinal cord hinders the evaluation of [18F]Fluoro-deoxy-glucose (FDG) uptake of the spinal cord in PET/CT. By exploiting the capability of MRI to precisely outline the spinal cord, we performed a retrospective study aimed to define normal pattern of spinal cord [18F]FDG uptake in PET/MRI. METHODS: Forty-one patients with lymphoma without clinical or MRI signs of spinal cord or bone marrow involvement underwent simultaneous PET and MRI acquisition using Siemens Biograph mMR after injection of 3.5 MBq/kg body weight of [18F]FDG for staging purposes. Using a custom-made software, we placed ROIs of 3 and 9 mm in diameter in the spinal cord, lumbar CSF, and vertebral marrow that were identified on MRI at 5 levels (C2, C5, T6, T12, and L3). The SUVmax, SUVmean, and the SUVmax and SUVmean normalized (NSUVmax and NSUVmean) to the liver were measured. For comparison, the same ROIs were placed in PET-CT images obtained immediately before the PET-MRI acquisition following the same tracer injection. RESULTS: On PET/MRI using the 3 mm ROI, the following average (all level excluding L3) spinal cord median (1st and 3rd quartile) values were measured: SUVmean, 1.68 (1.39 and 1.83); SUVmax, 1.92 (1.60 and 2.14); NSUVmean, 1.18 (0.93 and 1.36); and NSUVmax, 1.27 (1.01 and 1.33). Using the 9 mm ROI, the corresponding values were SUVmean, 1.41 (1.25-1.55); SUVmax, 2.41 (2.08 and 2.61); NSUVmean, 0.93 (0.79 and 1.04); and NSUVmax, 1.28 (1.02 and 1.39). Using the 3 mm ROI, the highest values of PET-MRI SUVmax, SUVmean, NSUVmax, and NSUVmean were consistently observed at C5 and the lowest at T6. Using a 9 mm ROI, the highest values were consistently observed at C5 and the lowest at T12 or T6. The spinal cord [18F]FDG-uptake values correlated with the bone marrow uptake at the same level, especially in case of NSUVmax. Comparison with PET-CT data revealed that the average SUVmax and SUVmean of the spinal cord were similar in PET-MRI and PET-CT. However, the average NSUVmax and NSUVmean of the spinal cord were higher (range 21-47%) in PET-MRI than in PET-CT. CONCLUSIONS: Using a whole-body protocol, we defined the maximum and mean [18F]FDG uptake of the normal spinal cord in PET/MRI. While the observed values show the expected longitudinal distribution, they appear to be higher than those measured in PET/CT. Normalization of the SUVmax and SUVmean of the spinal cord to the liver radiotracer uptake could help in multi-institutional comparisons and studies.
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Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) with different radiotracers enable regional evaluation of blood flow and glucose metabolism, of receptors and transporters of several molecules, and of abnormal deposition of peptides and proteins in the brain. The cerebellum has been used as a reference region for different radiotracers in several disease conditions. Whole-brain voxel-wise analysis is not affected by a priori knowledge bias and should be preferred. SPECT and PET have contributed to establishing the cerebellum role in motion, cognition, and emotion control in physiologic and pathophysiologic conditions. The basic abnormal imaging findings include decreased or increased uptake of flow or metabolism tracers in the cerebellum alone or as part of a network. Decreased uptake is generally observed in primary structural damage of the cerebellum, but can also represent a distant effect of cerebral damage (crossed diaschisis). Increased uptake can be observed in Freidreich ataxia, inflammatory or immune-mediated diseases of the cerebellum, and in status epilepticus. The possibility is also recognized that primary structural damage of the cerebellum might determine distance effects on other brain structures (reversed diaschisis). So far, SPECT and PET have been predominantly used in clinical studies to investigate cerebellar changes in neurologic and psychiatric diseases and in connection with pharmacologic, transcranial magnetic stimulation, deep-brain stimulation, or surgical treatments.
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Enfermedades Cerebelosas/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Medicina Nuclear , Cerebelo/efectos de los fármacos , Fluorodesoxiglucosa F18 , Humanos , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the main instruments for neuroimaging investigation of patients with chronic ataxia. MRI has a predominant diagnostic role in the single patient, based on the visual detection of three patterns of atrophy, namely, spinal atrophy, cortical cerebellar atrophy and olivopontocerebellar atrophy, which correlate with the aetiologies of inherited or sporadic ataxia. In fact spinal atrophy is observed in Friedreich ataxia, cortical cerebellar atrophy in Ataxia Telangectasia, gluten ataxia and Sporadic Adult Onset Ataxia and olivopontocerebellar atrophy in Multiple System Atrophy cerebellar type. The 39 types of dominantly inherited spinocerebellar ataxias show either cortical cerebellar atrophy or olivopontocerebellar atrophy. T2 or T2* weighted MR images can contribute to the diagnosis by revealing abnormally increased or decreased signal with a characteristic distribution. These include symmetric T2 hyperintensity of the posterior and lateral columns of the cervical spinal cord in Friedreich ataxia, diffuse and symmetric hyperintensity of the cerebellar cortex in Infantile Neuro-Axonal Dystrophy, symmetric hyperintensity of the peridentate white matter in Cerebrotendineous Xanthomatosis, and symmetric hyperintensity of the middle cerebellar peduncles and peridentate white matter, cerebral white matter and corpus callosum in Fragile X Tremor Ataxia Syndrome. Abnormally decreased T2 or T2* signal can be observed with a multifocal distribution in Ataxia Telangectasia and with a symmetric distribution in the basal ganglia in Multiple System Atrophy. T2 signal hypointensity lining diffusely the outer surfaces of the brainstem, cerebellum and cerebrum enables diagnosis of superficial siderosis of the central nervous system. The diagnostic role of nuclear medicine techniques is smaller. SPECT and PET show decreased uptake of radiotracers investigating the nigrostriatal system in Multiple System Atrophy and in patients with Fragile X Tremor Ataxia Syndrome. Semiquantitative or quantitative MRI, SPECT and PET data describing structural, microstructural and functional changes of the cerebellum, brainstem, and spinal cord have been widely applied to investigate physiopathological changes in patients with chronic ataxias. Moreover they can track diseases progression with a greater sensitivity than clinical scales. So far, a few small-size and single center studies employed neuroimaging techniques as surrogate markers of treatment effects in chronic ataxias.
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Ataxia , Encefalopatías , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Tomografía de Emisión de Positrones/métodos , Enfermedades de la Médula Espinal , Tomografía Computarizada de Emisión de Fotón Único/métodos , Ataxia/diagnóstico por imagen , Ataxia/patología , Ataxia/fisiopatología , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Encefalopatías/fisiopatología , Humanos , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/patología , Enfermedades de la Médula Espinal/fisiopatologíaRESUMEN
Occurrence of multiple primary lung cancers (MPLC) in individuals undergoing low-dose computed tomography (LDCT) screening has not been thoroughly addressed. We investigated MPLC in subjects recruited in the ITALUNG randomized clinical trial. Cases of cytologically/histologically proven MPLC detected at screening LDCT or follow-up CT were selected and pathologically re-evaluated according to the WHO 2015 classification. Overall 16 MPLC were diagnosed at screening LDCT (n=14, all present at baseline) or follow-up CT (n=2) in six subjects (4 in one subject, 3 in two and 2 in three subjects), representing 0.43% of the 1,406 screenees and 15.8% of the 38 subjects with at least one screen-detected primary lung cancer. MPLC included 9 adenocarcinomas in three subjects and a combination of 7 different tumour histotypes in three subjects. MPLC, mostly adenocarcinomas, are not uncommon in smokers and ex-smokers with at least one LDCT screen detected primary lung cancer.
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OBJECTIVE: To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. METHODS: Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. RESULTS: Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. CONCLUSIONS: In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.
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Encéfalo/patología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Reflejo Anormal/fisiología , Reflejo de Sobresalto/fisiología , Anciano , Encéfalo/diagnóstico por imagen , Femenino , Humanos , CintigrafíaRESUMEN
The presence of circulating tumor cells (CTC) or microemboli (CTM) in the peripheral blood can theoretically anticipate malignancy of solid lesions in a variety of organs. We aimed to preliminarily assess this capability in patients with pulmonary lesions of suspected malignant nature. We used a cell-size filtration method (ScreenCell) and cytomorphometric criteria to detect CTC/CTM in a 3 mL sample of peripheral blood that was taken just before diagnostic percutaneous CT-guided fine needle aspiration (FNA) or core biopsy of the suspicious lung lesion. At least one CTC/CTM was found in 47 of 67 (70%) patients with final diagnoses of lung malignancy and in none of 8 patients with benign pulmonary nodules. In particular they were detected in 38 (69%) of 55 primary lung cancers and in 9 (75%) of 12 lung metastases from extra-pulmonary cancers. Sensitivity of CTC/CTM presence for malignancy was 70.1% (95%CI: 56.9-83.1%), specificity 100%, positive predictive value 100% and negative predictive value 28.6% (95%CI: 11.9-45.3%). Remarkably, the presence of CTC/CTM anticipated the diagnosis of primary lung cancer in 3 of 5 patients with non-diagnostic or inconclusive results of FNA or core biopsy, whereas CTC/CTM were not observed in 1 patient with sarcoidosis and 1 with amarthocondroma. These results suggest that presently, due to the low sensitivity, the search of CTC/CTM cannot replace CT guided percutaneous FNA or core biopsy in the diagnostic work-up of patients with suspicious malignant lung lesions. However, the high specificity may as yet indicate a role in cases with non-diagnostic or inconclusive FNA or core biopsy results that warrants to be further investigated.
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PURPOSE: Timing and magnitude of blood release of circulating tumour cells (CTC) and circulating tumour microemboli (CTM) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer (NSCLC). METHODS: Twenty-eight consecutive patients with suspected stage III-IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy (FNAB). CTC and CTM (clusters of ≥3 CTC) were isolated by cell size filtration (ScreenCell), identified and counted by cytopathologists using morphometric criteria and (in 6 cases) immunostained for vimentin. RESULTS: FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood (mean 6.8 ± 3.7) was detected in 17 (65 %) and one CTM (mean 4.5 ± 3.3) in 15 (58 %) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously. CONCLUSIONS: CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.
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Adenocarcinoma/secundario , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/secundario , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/patología , Adenocarcinoma/metabolismo , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Vimentina/metabolismoRESUMEN
OBJECTIVES: To characterize early features of lung cancers detected with low-dose computed tomography (LDCT) screening. MATERIALS AND METHODS: Two radiologists reviewed prior LDCTs in 20 incident cancers diagnosed at annual repeat screening rounds and 83 benign nodules observed in the ITALUNG trial. RESULTS: No abnormality was observed in 3 cancers. Focal abnormalities in prior LDCT were identified in 17(85%) cancers (14 adenocarcinomas; 14 stage I). Initial abnormalities were intra-pulmonary in 10, subpleural in 4 and perifissural in 3. Average mean diameter was 9mm (range 4.5-18mm). Nine exhibited solid, 4 part-solid and 4 non-solid density. The margins were smooth and regular in 5 cases, lobulated in 6, irregular with spiculations in 3 and blurred in 3. Ten (59%) initial focal abnormalities had a round or oval nodular shape, but 7(41%) had a non-nodular complex (n=5) or "stripe-like" (n=2) shape. Bronchus sign was observed in 3 cases and association with cystic airspace in 2 cases. Non-solid density, complex or "stripe-like" shape, bronchus sign and association with cystic airspace had a specificity higher than 90%, but positive predictive value of every feature of incident lung cancers was low (range 10.4-50%). CONCLUSIONS: The vast majority of cancers diagnosed at annual repeat show corresponding focal lung abnormalities in prior LDCTs. Perifissural location and non-nodular shape do not exclude the possibility of early lung cancer. Since specificity of the early features of incident lung cancer is incomplete and their positive predictive value is low, all focal pulmonary abnormalities detected in screened subjects should be re-evaluated in subsequent LDCTs.
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Adenocarcinoma/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Ganglios Linfáticos/patología , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosAsunto(s)
Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Síndrome del Cromosoma X Frágil/complicaciones , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico por imagen , Trastornos Heredodegenerativos del Sistema Nervioso/patología , Anciano , Ataxia/diagnóstico por imagen , Ataxia/genética , Ataxia/patología , Atrofia/diagnóstico por imagen , Atrofia/genética , Atrofia/patología , Enfermedades de los Ganglios Basales/genética , Unión Competitiva/fisiología , Encéfalo/fisiopatología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/patología , Cuerpo Estriado/fisiopatología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Tractos Extrapiramidales/diagnóstico por imagen , Tractos Extrapiramidales/patología , Tractos Extrapiramidales/fisiopatología , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/diagnóstico por imagen , Mesencéfalo/patología , Mesencéfalo/fisiopatología , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Valor Predictivo de las Pruebas , Radiografía , Radioisótopos , Receptores Dopaminérgicos/metabolismo , Síndrome , Tomografía Computarizada de Emisión de Fotón Único , Temblor/diagnóstico por imagen , Temblor/genética , Temblor/patologíaRESUMEN
INTRODUCTION: Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography (LDCT). We report subjects' compliance and results of LDCT screening and management protocol in the active arm of the ITALUNG trial. METHODS: Three thousand two hundred six smokers or former smokers invited by mail were randomized to receive four annual LDCT (n = 1613) or usual care (n = 1593). Management protocol included follow-up LDCT, 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB). RESULTS: One thousand four hundred six subjects (87%) underwent baseline LDCT, and 1263 (79%) completed four screening rounds. LDCT was positive in 30.3% of the subjects at baseline and 15.8% subsequently. Twenty-one lung tumors in 20 subjects (1.5% detection) were found at baseline, and 20 lung tumors in 18 subjects (0.5% detection) in subsequent screening rounds. Ten of 18 prevalent (55%) and 13 of 17 incident (76%) non-small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects (42%), but at least one follow-up LDCT was obtained in 741 subjects (52.7%) over the screening period. FDG-PET obtained in 6.5% of subjects had 84% sensitivity and 90% specificity for malignant lesions. FNAB obtained in 2.4% of subjects showed 90% sensitivity and 88% specificity. Positivity of both FDG-PET and FNAB invariably predicted malignancy. Surgery for benign lesions was performed on four subjects (10% of procedures) but followed protocol violations on three subjects. CONCLUSIONS: High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance. Efficacy of screening is, however, weakened by low detection rate and specificity. Adhesion to management protocol might lessen surgery for benign lesions.
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Adenocarcinoma/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico , Ganglios Linfáticos/patología , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Tomografía Computarizada por Rayos X , Adenocarcinoma/cirugía , Anciano , Biopsia con Aguja Fina , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Carcinoma Pulmonar de Células Pequeñas/cirugía , Factores de TiempoRESUMEN
Imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET) have been widely applied to the investigation of patients with acute or chronic ataxias. Fundamentally, CT has a role in the emergency evaluation of the patient with acute ataxia to ascertain brainstem or cerebellar hemorrhage and to exclude a mass lesion in the posterior cranial fossa. Conventional MRI is the most frequently performed imaging investigation in patients with ataxia. It can support the diagnosis of acute cerebellitis and Wernicke encephalopathy by revealing T2 signal changes with a typical distribution. In patients with inherited or sporadic chronic ataxia it reveals three fundamental patterns of atrophy of the brainstem, cerebellum, and spinal cord which match the gross neuropathological descriptions. These are represented by olivopontocerebellar atrophy (OPCA), cortical cerebellar atrophy (CCA), and spinal atrophy (SA). A substantial correspondence exists among these patterns of atrophy shown by MRI and the etiological classification of inherited or acquired chronic ataxias. This, along with demonstration of T2 signal changes characteristic of some diseases, makes conventional MRI potentially useful for the diagnostic work-up of the single patient, especially in the case of a sporadic disease. Non-conventional MR techniques including diffusion MR, spectroscopy, and functional MR have been used in patients with acute or chronic ataxia, but their exact role in the evaluation of the single patient is not established yet. They are currently investigated as potential tools to monitor progression of neurodegeneration in chronic ataxia and to serve as "surrogate markers" in clinical trials. Several radiotracers have been utilized in combination with SPECT and PET in patients with ataxia. Perfusion SPECT can reveal cerebellar blood flow abnormalities early in the course of cerebellitis. It has also been utilized to investigate perfusion of the brain in several inherited or sporadic chronic ataxic diseases, contributing to improved understanding of the pathophysiology of these conditions. Recently, perfusion SPECT has been tested as a "surrogate marker" to verify the effects of newly developed therapies in patients with a variety of chronic ataxias. Whole-body FDG-PET is recommended in patients with suspected paraneoplastic cerebellar degeneration to detect the primary malignancy. Brain FDG-PET has provided important information on the pathophysiology of several acquired and inherited conditions. PET and SPECT with radiotracers able to assess the nigrostriatal system or the density of D2 dopamine receptors in the striatum are increasingly used in patients with adult-onset sporadic ataxia for the differential diagnosis between multiple system atrophy in which overt striatal abnormalities are found and idiopathic late-onset cerebellar ataxia in which no abnormality is detected.