Angelo Del Sole

Anatomical and biochemical investigation of primary brain tumours

Cancerous transformation entails major biochemical changes including modifications of the energy metabolism of the cell, e.g. utilisation of glucose and other substrates, protein synthesis, and expression of receptors and antigens. Tumour growth also leads to heterogeneity in blood flow owing to focal necrosis, angiogenesis and metabolic demands, as well as disruption of transport mechanisms of substrates across cell membranes and other physiological boundaries such as the blood-brain barrier. All these biochemical, histological and anatomical changes can be assessed with emission tomography, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Whereas anatomical imaging is aimed at the diagnosis of brain tumours, biochemical imaging is better suited for tissue characterisation. The identification of a tumoural mass and the assessment of its size and vascularisation are best achieved with X-ray CT and MRI, while biochemical imaging can provide additional information that is crucial for tumour classification, differential diagnosis and follow-up. As the assessment of variables such as water content, appearance of cystic lesions and location of the tumour are largely irrelevant for tissue characterisation, a number of probes have been employed for the assessment of the biochemical features of tumours. Since biochemical changes may be related to the growth rate of cancer cells, they can be thought of as markers of tumour cell proliferation. Biochemical imaging with radionuclides of processes that occur at a cellular level provides information that complements findings obtained by anatomical imaging aimed at depicting structural, vascular and histological changes. This review focusses on the clinical application of anatomical brain imaging and biochemical assessment with positron emission tomography, single-photon emission tomography and MRS in the diagnosis of primary brain tumours, as well as in follow-up.

Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients

BackgroundHIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.MethodsBone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression.Results78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05).ConclusionsHeightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.

Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone

The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

Double-blind stereo-EEG and FDG PET study in severe partial epilepsies: Are the electric and metabolic findings related?

The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.

Overview of presurgical assessment and surgical treatment of epilepsy from the Italian League Against Epilepsy

The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.

Comparative analysis of cadmium-zincum-telluride cameras dedicated to myocardial perfusion SPECT: A phantom study

BackgroundThis investigation used image data generated by an anthropomorphic phantom with a cardiac insert for a comparison between two solid state cameras: D-SPECT and D530c.MethodsFor each camera, two sets (with and without a simulated transmural defect (TD)) of scans were acquired starting from the in vivo standard count statistics in the left ventricle (LV). Other two acquisitions corresponding to 150% and 50% of the reference count statistics were acquired. Five performance indices related to spatial resolution, contrast, and contrast-to-noise ratio (CNR) were analyzed.ResultsD-SPECT showed a lower LV wall thickness and an inferior sharpness than D530c. No significant differences were found in terms of contrast between LV wall and the inner cavity, TD contrast or CNR. No significant differences were observed in CNR when moving from the reference level of count statistics down to 50% or up to 150% of the counts acquired on the LV.ConclusionsOur results show that D-SPECT and D530c have different performances. The lack of differences in the image performance indices along the range of count statistics explored, indicates that there is the possibility for a further reduction in the injected activity and/or the acquisition time, for both systems.

Appropriate use of positron emission tomography with [18F]fluorodeoxyglucose for staging of oncology patients

Positron emission tomography (PET) was developed in the mid-1970, and its initial applications were for heart and brain imaging research. Nowadays, this technology is aimed mainly at staging or restaging tumours as it allows the assessment of biochemical processes that are either specific or associated with tumour biology. The full appreciation of PET potentials and limitations among general practitioners and internists cannot be considered achieved and the appropriate use of PET especially when coupled to X-ray computed tomography (CT) is still suboptimal. The majority of PET studies rely on the use of fluorodeoxyglucose labelled with fluorine-18 (FDG), which is a radiopharmaceutical specific for glucose transport and metabolism. PET with FDG is amenable for studying most type of tumours, including those of the head and neck, lung, oesophagus, colo-rectal, gastrointestinal stromal tumours, pancreas, some types of lymphomas and melanoma, whereas in some tumours, including those of the reproductive system, brain, breast and bones, there is a limited role for PET and there is no substantial role for FDG-PET for the bronchoalveolar, hepatocellular, urinary system, testicular, neuroendocrine, carcinoids and adrenal tumours, differentiated thyroid cancers, and several subtypes of malignant lymphoma. Thus, the limits of FDG have stimulated the use and development of other radiopharmaceuticals. These tracers represent the opportunity for expanding the use of PET to other areas in oncology in the near future.

Correlation between 123I-FP-CIT brain SPECT and parkinsonism in dementia with Lewy bodies: caveat for clinical use.

Introduction Although parkinsonism is considered a core feature of dementia with Lewy bodies (DLB), it is occasionally mild or even absent. 123I-FP-CIT SPECT has been accepted as a diagnostic support tool in this context, given that low striatal uptake is associated with neuronal loss. The aim of this retrospective study was to look for correlations between 123I-FP-CIT uptake in the striatum and clinical extrapyramidal signs (EPSs) in patients with a diagnosis of probable DLB to clarify the extent to which the supporting role of 123I-FP-CIT is related to motor impairment. Methods Semiquantitative 123I-FP-CIT uptake was analyzed and correlated with Unified Parkinson Disease Rating Scale Part III scores in a sample of 22 patients with a diagnosis of probable DLB and a wide range of EPSs. Results A significant negative linear correlation between 123I-FP-CIT uptake and Unified Parkinson Disease Rating Scale Part III score was found both in the caudate and the putamen (r = −0.69 and −0.72, respectively, P < 0.001). Striatal uptake in patients with no or questionable EPS was comparable to that recorded in normal age-matched subjects (99% [22%] in the putamen) but significantly reduced in those with mild and severe EPS (43% [35%] and 30% [17%], respectively, P < 0.0001, but P = nonsignificant between mild and severe EPS). Conclusions SPECT may be redundant when there are no doubts about the parkinsonism (ie, when it is absent or unequivocally present), but it may be helpful in identifying presynaptic nigrostriatal degeneration in patients with mild EPSs.

Response to Treatment: the Role of Imaging

Cancer is a major human health problem, both in developing and developed countries. While screening and improved therapies have yielded relevant successes for some forms of cancer—resulting in a 1% annual decline in mortality from all cancers in the USA since 1990—each year, about 7 million people worldwide and 600,000 in the USA continue to die from this disease [1].

In vivo neurochemistry with emission tomography and magnetic resonance spectroscopy: clinical applications

Abstract. The assessment of neurochemical processes in vivo has received much attention in the past decade as techniques such as positron or single photon emission tomography (PET and SPET), and magnetic resonance spectroscopy (MRS) have become more available. With PET and SPET, basic processes, such as blood flow and oxygen or glucose metabolism, can be regionally assessed, along with more specific functions such as the production, release, and reuptake of neurotransmitters and their occupancy of specific receptors. At the same time, MRS can reveal changes in concentration of several hydrogenate compounds in the brain. All these methods have been extensively applied for research in neurology, and some applications have reached the clinical level, namely for the study of degenerative diseases, motor-neuron diseases, movement disorders, cerebrovascular diseases, and epilepsy. This article focuses on the most relevant information that can be obtained with these complementary techniques to help clinicians in the assessment of neurological diseases.