Correlation between Apolipoprotein E genotype and brain metabolism in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment. METHODS: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates. RESULTS: Brain metabolism was significantly positively correlated with APOE genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme. CONCLUSIONS: We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

Primary CNS Lymphomas: Challenges in Diagnosis and Monitoring.

Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm that can involve brain, eye, leptomeninges, and rarely spinal cord. PCNSL lesions most typically enhance homogeneously on T1-weighted magnetic resonance imaging (MRI) and appear T2-hypointense, but high variability in MRI features is commonly encountered. Neurological symptoms and MRI findings may mimic high grade gliomas (HGGs), tumefactive demyelinating lesions (TDLs), or infectious and granulomatous diseases. Advanced MRI techniques (MR diffusion, spectroscopy, and perfusion) and metabolic imaging, such as Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or amino acid PET (usually employing methionine), may be useful in distinguishing these different entities and monitoring the disease course. Moreover, emerging data suggest a role for cerebrospinal fluid (CSF) markers in predicting prognosis and response to treatments. In this review, we will address the challenges in PCNSL diagnosis, assessment of response to treatments, and evaluation of potential neurotoxicity related to chemotherapy and radiotherapy.

18F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: a pilot study / 18F-FDG PET/TC, cirugía citorreductora y quimiohipertermia intraperitoneal para el tratamiento terapéutico de la carcinomatosis peritoneal: estudio piloto

Aim. Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal18F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. Methods. Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery 18F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. Results. 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by 18F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased 18F-FDG uptake, were recognized. Conclusions. PP + IPCH of patients selected by 18F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients (AU)

Objetivo. La carcinomatosis peritoneal es una evolución común de las neoplasias y constituye el estadio terminal de la enfermedad. Se ha desarrollado una nueva técnica, basada en la extirpación quirúrgica de las lesiones peritoneales (procedimiento de peritonectomía - PP), combinada con quimiohipertermia intraperitoneal (IPCH). La adecuada selección de los pacientes es primordial, a fin de optimizar los resultados del tratamiento. El objetivo de este estudio fue investigar el papel de la tomografía de emisión de positrones con [(18)F]fluoro-2-deoxy-d-glucosa/tomografía computarizada (18F-FDG PET/TC) en pacientes con carcinomatosis peritoneal, seleccionados para someterse a PP e IPCH. Además, tratamos de identificar los patrones característicos de la captación abdominal de 18F-FDG y correlacionar dichos patrones con los hallazgos anatómicos disponibles tras la cirugía. Métodos. Se realizaron exámenes 18F-FDG PET/TC de manera prospectiva, y previamente a la cirugía, a los pacientes con carcinomatosis peritoneal histológicamente confirmada, o sospechada mediante seguimiento clínico y/o hallazgos de imagen. Solo puede tratarse con PP y IPCH a aquellos pacientes que no reflejen evidencia de metástasis extraperitoneales en los exámenes PET/TC. Resultados. Se seleccionó para el estudio a 11 pacientes con carcinomatosis peritoneal (5 colorrectales, 4 ováricas, una pancreática) y un cáncer primitivo desconocido. En todos los casos, el examen PET/TC reflejó múltiples implantes peritoneales. En 6 de los 11 casos (54%) las metástasis fueron evidenciadas mediante 18F-FDG PET/TC: 2 casos con metástasis hepáticas, un caso con metástasis óseas, y 3 pacientes con lesiones ganglionares. Se reconocieron 2 patrones de imagen distintos, con aumento de captación focal o difusa de 18F-FDG. Conclusiones. La combinación PP + IPCH de los pacientes seleccionados mediante 18F-FDG PET/TC parece ser una técnica segura y factible. La PET/TC se revela como una herramienta fiable para la detección y caracterización de los implantes peritoneales, con un impacto potencial sobre el tratamiento terapéutico de dichos pacientes (AU)

(18)F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: A pilot study.

AIM: Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography ((18)F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal(18)F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. METHODS: Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery (18)F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. RESULTS: 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by (18)F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased (18)F-FDG uptake, were recognized. CONCLUSIONS: PP+IPCH of patients selected by (18)F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients.

Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The neurodegenerative process results in progressive muscle paralysis and even in cognitive impairment. Within the complex diagnostic work-up, positron emission tomography (PET) represents a valuable imaging tool in the assessment of patients with ALS. PET, by means of different radiotracers (i.e. 18F-fluorodeoxyglucose, 6-[18F]fluoro-L-dopa, [11C]flumazenil) can assess the status of the wide range of brain regions and neural circuits, which can be affected by ALS. Furthermore, experimental radiocompounds have been developed for the evaluation of white matter, which plays a role in the progression of the disease. Here we present a comprehensive review including in different sections the most relevant PET studies: studies investigating ALS and ALS-mimicking conditions (especially primary lateral sclerosis and other neurodegenerative diseases), articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients.

Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: What 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report / Síndrome linfoproliferativo autoinmune indefinido y linfoma no-Hodgkin. ¿Qué puede aportar la exploración 18F-FDG-PET/CT al tratamiento de estos pacientes? Sugerencias a partir de un caso

A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A 18F-FDG-PET/CT scan showed many areas of intense 18F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the 18F-FDG-PET/CT scan showed a complete metabolic response (AU)

Un paciente joven con síndrome linfoproliferativo autoinmune indefinido (ALPS-U) y dolor lumbar se sometió a una tomografía computarizada y a una resonancia magnética, estudios que mostraron varias lesiones vertebrales, algunos nódulos pulmonares y adenopatías laterocervicales difusas. Una exploración 18F-FDG-PET/TC reveló áreas de captación intensa de 18F-FDG en múltiples vértebras, algunas costillas, sacro, hígado, ambos pulmones y en varios ganglios linfáticos repartidos en las cadenas cervicales, torácica y abdominal. La biopsia de médula ósea diagnosticó una “granulomatosis linfomatoide”, una variante poco frecuente de Linfoma no-Hodgkin de células B (LNH). Tras el tratamiento, la exploración 18F-FDG-PET/TC demostró una respuesta metabólica completa (AU)

Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response.

PET/CT imaging in neuroblastoma.

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

A distinct MR imaging phenotype in amyotrophic lateral sclerosis: correlation between T1 magnetization transfer contrast hyperintensity along the corticospinal tract and diffusion tensor imaging analysis.

BACKGROUND AND PURPOSE: In the search for a diagnostic marker in ALS, we focused our attention on the hyperintense signal intensity in T1 MTC MR images along the CST, detected in some patients and not found in other patients with ALS and in control subjects. The aim of this study was to investigate the relationship between the hyperintense signal intensity in T1 MTC images and white matter damage. To this purpose, we studied potential heterogeneities in DTI values within our patients by using TBSS without a priori anatomic information. MATERIALS AND METHODS: In 43 patients with ALS and 43 healthy control subjects, the presence or absence of T1 MTC hyperintense signal intensity was evaluated. With a DTI analysis with a TBSS approach, differences in FA distribution between the 2 groups (patients with T1 MTC hyperintense signal intensity and patients without it) compared with each other and with control subjects were investigated. RESULTS: We found regional differences in white matter FA between patients with T1 MTC hyperintense signal intensity (37.2%) and patients without it. Patients with T1 MTC abnormal signal intensity showed lower FA strictly limited to the motor network and the posterior aspect of the body of the CC without extramotor FA reductions, whereas patients without this sign showed FA reductions in several confluent regions within and outside the CST and in the whole CC. CONCLUSIONS: T1 MTC hyperintense signal intensity in the CST and posterior CC, when present, is specific for ALS and represents, among patients with ALS, a possible distinct phenotype of presentation of the disease with prominent UMN involvement.

PET in the clinical work-up of patients with spondylodiscitis: a new tool for the clinician?

AIM: The role of 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) in the clinical management of patients with inflammatory diseases (e.g., chronic inflammatory diseases, fever of unknown origin, ostemyelitis, prosthesis infections) is still under investigation. The aim of the present study was to evaluate the usefulness of PET in the diagnostic work-up of patients with spondylodiscitis and to compare it with magnetic resonance imaging (MRI). METHODS: This retrospective study included 33 patients with suspected/confirmed spondylodiscitis. Two groups were created: 1) disease definition (n=24); and 2) treatment assessment (N.=16, 21 exams). Disease status was defined on the basis of data collected for symptoms, hematological parameters, imaging studies and histological findings, when available. Qualitative and semiquantitative analysis of the PET images was performed. The minimum duration of follow-up was 6 months. RESULTS: For the Disease Definition group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92.9%, 50%, 72.2%, 83.3%, and 75%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 50%, 76.9%, 100%, and 81.3%, respectively. For the Treatment Assessment group, FDG-PET showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 90%, 81.8%, 81.8%, 90%, and 85.7%, respectively, and MRI showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 16.7%, 58.3%, 100% and 61.5%, respectively. No significant differences were observed between qualitative and semiquantitative evaluation of PET scans. CONCLUSION: PET and MRI showed similar accuracy in the diagnosis of spondylodiscitis, indicating that PET can be used when MRI is doubtful or unavailable. PET was more accurate and more specific than MRI in treatment assessment, suggesting that PET should be preferred over MRI for determining when treatment can be safely discontinued.

Breast cancer cellular proliferation indexes and 99mTc-sesta Mibi capture: what correlation?

Aim of this study was to verify existing correlations between breast cancer 99mTc-sestaMIBI cells uptake and their cytological characteristics. Forty-five patients with clinically and/or mammographically suspect breast cancer were enrolled. In all patients 99mTc-sestaMIBI scintimammography was performed and malignant lesions were detected in 44 cases and benign in one case. In positive uptake (PU) lesions with diameter <1.5cm, 85.7% showed a high tumor grade (II-III degrees) while in negative uptake (NU) lesions with diameter <1.5cm, 100% showed a low tumor grade (I degrees). In PU lesions, 70% had expressed a high value of Ki 67, while 100% of the NU lesions showed normal values. In this series, tumor diameter does not play a basic role, while the correlations between uptake and the histological grade (G) and/or cellular kinetics (Ki67) seem to be more important. Further studies are needed to confirm our present results.

[Breast carcinoma and the axillary lymph node status: the use of 99mTc-sestamibi scintimammography for the diagnosis and preoperative staging. Preliminary results]. / Il carcinoma mammario e lo status linfonodale ascellare: uso della 99mTc sestaMIBI scintimammografia a scopo diagnostico e stadiativo prechirurgico. Risultati preliminari.

BACKGROUND: The purpose of this study is the sensitivity and specificity evaluation of the 99mTc-sestaMIBI scintimammography (SMM) in the diagnosis and pre-surgical staging of patients with clinical and/or radiological suspicion of breast cancer. MATERIALS AND METHODS: Forty-five patients with clinical and/or mammographic breast cancer suspicion were enrolled. Prone lateral views of both mammalian glands and anterior of chest, to evaluate the axillary lymph node infiltration, were acquired 60 min after i.v. injection of 20-25 mCi of 99mTc-sestaMIBI. RESULTS: Breast cancer was diagnosed by histological findings in 44 patients; benign disease in 1 case. The tumors diameter ranged from 0.3 to 4 cm. The SMM sensitivity in the detection of breast cancer was 90% and the VPP was 100%. The smallest diameter in these detected lesions was 0.5 cm. The pathologic examination showed metastatic axillary involvement in 15 patients. The SMM sensitivity in the detection of axillary lymph node metastases was 75%, specificity was 90%. For each lesion grading, mitosis number, 67Ki expression, diameter, were considered and correlated to 99mTC-sestaMIBI uptake. The 5 breast cancer non-uptake cases had low cytoproliferative indexes. According to our data it is possible to observe that there is a correlation between uptake and cellular proliferation. CONCLUSIONS: The 99mTc-sestaMIBI SMM is a highly accuracy test in the breast cancer detection. The sensitivity in the axillary lymph node metastatic detection is just little below average according to the literature; it is possible that the results can improve with higher accrual of patients, operator experience and equipment improvement and the using of SPECT.