Nuclear Medicine Techniques Research Articles

Use of 99mTc-labelled Anti-TNF Monoclonal Antibodies to Assess Patients Affected by Inflammatory Arthropathies

Nuclear medicine techniques have been applied for many years to assess the activity in patients with different inflammatory arthropathies. The recent development of specific radiopharmaceuticals suggested the possibility to use nuclear medicine in order to clarify the disease mechanisms and predict response to treatment. In this review, we aimed at presenting data concerning the use of 99mTc-labelled anti-TNF monoclonal antibodies. Few studies have been conducted in patients affected by Rheumatoid Arthritis and Spondyloarthropathies, treated for systemic or mono-articular involvement, showing the possible use of this specific scintigraphy.

Nuclear medicine techniques in Merkel cell carcinoma: A case report and review of the literature.

Merkel cell carcinoma (MCC) is a rare and aggressive type of neuroendocrine cancer of the skin. It predominantly affects the elderly, with a predilection for the sun-exposed skin of the head and neck. Risk factors include immune-suppressing diseases, such as human immunodeficiency virus (HIV), chronic lymphocytic leukemia and multiple myeloma, organ transplantation, and the presence of the newly-identified Merkel cell polyomavirus (MCPyV). Diagnosis is based on pathological findings, primarily the immunohistochemical determination of cytokeratin 20 positivity. By contrast, staging relies on conventional imaging methods, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging, and nuclear medicine techniques, such as sentinel lymph node scintigraphy, somatostatin receptor scintigraphy (SRS), and positron emission tomography (PET)/CT with 18F-fluorodeoxyglucose (FDG) or alternative radiopharmaceuticals. The treatment of MCC is primarily surgical, with possible adjuvant radiation, while the use of chemotherapy appears to be an alternative therapeutic option that is used only in specific cases. The present study describes the case of a 43-year-old HIV-positive Caucasian man with MCC located on the posterior surface of the left thigh, which was identified by cytological and histological examination of tissue sampled by fine needle aspiration and biopsy performed under CT. SRS demonstrated a high uptake of 111In-diethylene triamine pentaacetic acid-octreotide at the affected site. Therefore, the lesion was surgically excised, and the patient received chemotherapy and adjuvant radiotherapy. Three months subsequent to treatment, the patient underwent a PET/CT scan with 18F-FDG that demonstrated uptake in the cervical lymph nodes and the area of the excised lesion. These findings indicated that the disease was in remission. The aim of the present study was to highlight the value and contribution of nuclear medicine in the diagnosis, staging and follow-up, using PET/CT, octreoscan and sentinel lymph node scintigraphy, of patients with MCC, as well as the therapeutic strategy of radiolabelled somatostatin analogue scintigraphy.

Modern radionuclide methods in diagnosing orbital masses

Anatomic and topographic features of orbit structure and similar clinical symptoms in many diseases of different etiologies explain the complicated early diagnosis of orbital diseases. Therefore, the diagnostic algorithm for orbital masses is mainly based on instrumental diagnostic methods, especially radiology. Over the past 20-30 years, radiologic diagnosis of orbital tumors took a step forward thanks to the introducing such methods as computer tomography, magnetic resonance imaging and ultrasound into clinical practice. However, these methods of investigation, despite their great diagnostic possibilities, not always allow to obtain objective information on the tumor biology, tumor malignancy grade and characteristics of their metabolism. A significant step forward in this direction was the development and introduction of modern nuclear medicine techniques such as single photon emission computed tomography and positron emission (two-photon) tomography into clinical practice. These methods allow to visualize the functional processes in normal conditions and to perform a kind of non-invasive biopsy in case of neoplastic disorders. The use of nuclear medicine in oncology is based on hyperfixation of some radiopharmaceuticals in malignant tumors that provides important data for diagnosis and differential diagnosis based on the study of physiological and biological tumor features. The review highlights brief historical facts, as well as the results of using the most informative and safe radiopharmaceuticals. Literature analysis concludes that radionuclide tests at some point might be a method of choice for differential diagnosis of orbital masses.

Nuclear imaging in the diagnosis of primary aldosteronism.

Purpose of reviewPrimary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical ‘Conn's adenoma’) offers the potential for curative adrenalectomy. Adrenal vein sampling (AVS), in conjunction with cross-sectional imaging, remains the ‘gold standard’ for distinguishing unilateral and bilateral disease, but is technically demanding and frequently unsuccessful or inconclusive. As such, alternative strategies for lateralization, including nuclear medicine techniques, are being developed and brought into clinical practice.Recent findingsMetomidate, a potent ligand of CYP11B1 and CYP11B2, can be C11H3-labelled as a PET tracer and has been shown to offer a rapid noninvasive alternative to AVS for localizing unilateral aldosterone-producing adenomas.SummaryIncreasing experience with 11C-metomidate PET-CT supports its use as an adjunct to AVS when this has failed, is ambiguous, or cannot be undertaken.

Nuclear medicine imaging in bone metastases

Nuclear medicine techniques designed to identify bone metastases are reviewed. They include planar and whole body, single photon emission tomography (SPET), F-18 Fluorine and FDG, deoxyglucose, positron emission tomography (PET), bone imaging.

Dilemma in diagnosing thyroid adenoma – A case report

A thyroid adenoma is a benign tumour of the thyroid gland. Almost all thyroid adenomas are follicular adenomas. In the clinical management of such patients, the extent of surgery depends on whether it is truly a follicular adenoma or a follicular carcinoma. In case of follicular adenomas where Fine Needle Aspiration (FNA) findings are inconclusive, nuclear medicine techniques play an important role in the pre operative work up. Here we present a case of follicular adenoma highlighting the role of nuclear medicine techniques in the pre operative workup along with the diagnostic dilemmas that can occur DOI: http://dx.doi.org/10.3329/bjnm.v17i1.22497 Bangladesh J. Nuclear Med. 17(1): 91-96, January 2014

Imaging in Tuberculosis

Despite many advances in both diagnosis and treatment, tuberculosis still remains one of commonest causes of morbidity and mortality from any infectious cause in the world. Although the overall incidence and mortality rate for tuberculosis has decreased over the years, timely and accurate diagnosis of tuberculosis is essential for the health of the patient as well as the public. For the diagnosis of tuberculosis, a high degree of clinical suspicion is required, and this becomes much more important in high-risk populations. Tuberculosis may masquerade as any disease; therefore, tissue and microbiological assessment is sometimes important for establishing the diagnosis. However, in daily practice, the clinician and radiologist should be familiar with the imaging features of pulmonary and extrapulmonary tuberculosis, as well as manifestations of tuberculosis in immunocompromised patients. Imaging provides a very important role in the diagnosis and management of tuberculosis. Although chest X rays remain the basic imaging modality for pulmonary tuberculosis, computed tomography, magnetic resonance imaging, and nuclear medicine techniques, including positron emission tomography/computed tomography, are extremely helpful in the assessment of both pulmonary and extrapulmonary tuberculosis.

Locally sparse reconstruction using the $l^{1,\infty}$-norm

This paper discusses the incorporation of local sparsity information, e.g. ineach pixel of an image, via minimization of the $\ell^{1,\infty}$-norm. Wediscuss the basic properties of this norm when used as a regularizationfunctional and associated optimization problems, for which we derive equivalentreformulations either more amenable to theory or to numerical computation.Further focus of the analysis is put on the locally 1-sparse case, which iswell motivated by some biomedical imaging applications. Our computational approaches are based on alternating direction methods ofmultipliers (ADMM) and appropriate splittings with augmented Lagrangians. Thoseare tested for a model scenario related to dynamic positron emissiontomography (PET), which is a functional imaging technique in nuclear medicine. The results of this paper provide insight into the potentialimpact of regularization with the $\ell^{1,\infty}$-norm forlocal sparsity in appropriate settings. However, it alsoindicates several shortcomings, possibly related to the non-tightness of thefunctional as a relaxation of the $\ell^{0,\infty}$-norm.

Metastatic Medullary Thyroid Cancers: Challenges in Diagnosis with Nuclear Medicine Techniques and the Role of Radionuclide Therapy

Medullary thyroid cancer is a rare tumor driven from neuroendocrine cells. In the last decade there has been important discoveries regarding its genetics and relationship between genotype and phenotype on familial cases. However remains unknown the best approach for patient with maintained high levels of tumor markers such as calcitonin. Most available imaging techniques are able to accurately find metastatic lesions only in advanced disease. Traditionaly, nuclear medicine images are able to find metastatic suspicious lesions before they reach the size to be considered suspicious in conventional studies such as computed tomography scans or magnetic resonance imaging. However in patients with medullary thyroid cancer the ideal radiopharmaceutical for this purpose is yet to be found. Based on the biology of the tumor, some radiopharmaceuticals have been studied for diagnosis and also for therapy in those patients. The aim of this review is to describe the radiopharmaceuticals used for diagnosis and treatment until today and the role of each of them in medical care. In conclusion, the medullary thyroid cancer is a rare tumor and the review shows that despite all studies there is still no consensus on the importance of nuclear medicine in the diagnosis and treatment of these patients. Further studies are still needed.

Nuclear medicine in diagnosis of prosthetic valve endocarditis: an update.

Over the past decades cardiovascular disease management has been substantially improved by the increasing introduction of medical devices as prosthetic valves. The yearly rate of infective endocarditis (IE) in patient with a prosthetic valve is approximately 3 cases per 1,000 patients. The fatality rate of prosthetic valve endocarditis (PVE) remains stable over the years, in part due to the aging of the population. The diagnostic value of echocardiography in diagnosis is operator-dependent and its sensitivity can decrease in presence of intracardiac devices and valvular prosthesis. The modified Duke criteria are considered the gold standard for diagnosing IE; their sensibility is 80%, but in clinical practice their diagnostic accuracy in PVE is lower, resulting inconclusively in nearly 30% of cases. In the last years, these new imaging modalities have gained an increasing attention because they make it possible to diagnose an IE earlier than the structural alterations occurring. Several studies have been conducted in order to assess the diagnostic accuracy of various nuclear medicine techniques in diagnosis of PVE. We performed a review of the literature to assess the available evidence on the role of nuclear medicine techniques in the diagnosis of PVE.

Multimodal Imaging in Lung Cancer: It Is Time to Change

The imaging techniques can be classified into two main groups: Structural/morphological imaging (SMI), which includes X rays (XR), computed tomography (CT), ultrasounds (US) as well as some varieties of magnetic resonance (MRI), and shows anatomic-morphological aspects, and molecular imaging (MI), which includes nuclear medicine (SPECT, PET), fMRI, optical and nanosystems techniques, and provides information about biochemistry/biological activity, often before structural changes. According to Society of Nuclear Medicine and Molecular Imaging, MI “is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems”. MI procedures are noninvasive, safe and painless. Its sensitivity is greater than SMI, but it lacks anatomical detail, which has led to the development of multimodal imaging, combining structural and molecular techniques, widely used at present in daily practice. The pillars of MI are biochemistry/biology, instrumentation and software, and its cycle is the following: study of biology/biochemistry of a process, establishment/definition of specific targets, and development of tracers, preclinical imaging, histological validation and finally clinical imaging. This new concept led to the individualized diagnostic and treatment, being the patient the center of the medical activity. “As opposed to the doctor-centric, curative model of the past, the future is going to be patient-centric and proactive” said Dr. Zerhouni (NIH Medline Plus Winter 2007). The doctor must adapt to the needs of the own patient and this fact requires a true change of heart, because MI is intimately tied to the biology of the disease to analyzing. A new and strong interrelationship came into being: a bidirectional system biology-imaging that will allow to be much more effective in the daily practice, not only in relation to diagnosis (specific and early), but also with therapy (guide cancer treatment selection and evaluate early treatment response). There is an absolute necessity to lock the two together. Likewise, in the future the biology of a disease will indicate us what is the most adequate imaging technique and vice versa. In this regard, we know that in non-small cell lung cancer (NSCLC), ALK+ status is associated with distinct characteristics at CT imaging (CT radiogenomic characterization) [1], and that in lung adenocarcinomas 18F-FDG uptake values are related with expression levels of cellular Glucose Transporters and EGFR mutations. For this reason, different EGFR mutations correlate with different FDG uptake values.

The Significance of Cerebral Hemodynamics Imaging in Carotid Endarterectomy: A Brief Review

The indication of carotid endarterectomy (CEA) is principally determined by the presence or absence of symptoms and the degree of stenosis. However, the results of recent studies have implicated the usefulness of cerebral hemodynamics imaging for perioperative assessments. Many studies using single-photon emission computed tomography (SPECT) have demonstrated that cerebral hemodynamics imaging assessments are useful in the prediction and assessment of post-CEA hyperperfusion. In studies using transcranial Doppler ultrasonography, SPECT, or positron-emission tomography (PET), cerebral hemodynamic impairment is highly likely to increase the risk of cerebral infarction in patients with asymptomatic carotid artery stenosis. In other studies using the same modalities, cerebral hemodynamic impairment might be related to cognitive impairment in carotid artery stenosis, and this cognitive impairment might be improved with CEA. Nuclear medicine techniques involve the injection of radioactive tracers. Arterial spin labeling (ASL) is an emerging technique of perfusion magnetic resonance imaging (MRI) for the noninvasive measurement of cerebral perfusion. ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion activities that are equivalent to SPECT. In addition, regional perfusion imaging visualizes cerebral perfusion territories by selective ASL. In conclusion, cerebral hemodynamic imaging would be useful for the perioperative assessment of CEA. However, there is a lack of sufficient scientific evidence to confirm the benefits, necessitating further study.

A review of performance of near-infrared fluorescence imaging devices used in clinical studies.

Near-infrared fluorescence (NIRF) molecular imaging holds great promise as a new "point-of-care" medical imaging modality that can potentially provide the sensitivity of nuclear medicine techniques, but without the radioactivity that can otherwise place limitations of usage. Recently, NIRF imaging devices of a variety of designs have emerged in the market and in investigational clinical studies using indocyanine green (ICG) as a non-targeting NIRF contrast agent to demark the blood and lymphatic vasculatures both non-invasively and intraoperatively. Approved in the USA since 1956 for intravenous administration, ICG has been more recently used off label in intradermal or subcutaneous administrations for fluorescence imaging of the lymphatic vasculature and lymph nodes. Herein, we summarize the devices of a variety of designs, summarize their performance in lymphatic imaging in a tabular format and comment on necessary efforts to develop standards for device performance to compare and use these emerging devices in future, NIRF molecular imaging studies.

Diagnostic Imaging in Dermatology: Utility of PET-CT in Cutaneous Melanoma

Malignant melanoma accounts for 5% of all malignant skin tumors and its incidence is increasing. In the natural course of melanoma, tumors grow locally and can spread via the lymph system or the blood. Because survival is directly related to the stage of the disease at diagnosis, early detection (secondary prevention) has an impact on prognosis. Positron emission tomography (PET) is a nuclear medicine technique that generates images using molecules labeled with positron-emitting isotopes. The most widely used molecule is fluorodeoxyglucose (FDG). Because of the elevated glycolytic rate in tumor cells, which results in increased FDG uptake, greater quantities of FDG become trapped in tumor cells, enabling external detection. Today, most PET scanners are multimodal PET–computed tomography (CT) scanners, which provide more detailed information by combining morphological information with functional PET findings. The possible utility of PET-CT in patients with malignant melanoma is a subject of debate. Various questions have been raised: when the scan should be performed, whether PET-CT has advantages over conventional diagnostic methods, and whether PET-CT provides a real benefit to patients. In this review of the literature, we will analyze each of these questions.

A strategy to reduce blocky pattern and contrast loss in emission tomography reconstruction with reduced angular sampling and total variation minimization

Purpose Reducing radiation dose or scanning time is important for patient safety when using nuclear medicine technique. The aim of this study is to develop a reconstruction method to suppress deterioration of image quality with only a small sampling number of projection data in single photon emission computed tomography (SPECT).

Imaging techniques in the characterization of adrenal lesions.

Radiol Bras. 2014 Nov/Dez;47(6):V–VI Currently, with the increasing utilization of sectional imaging methods, most adrenal masses are incidentally found during imaging investigation performed for other indications. Non-functional adenomas constitute the majority of incidentally found adrenal masses. However, the suprarenal gland is also a common site of metastasis and less frequently primary tumors including myelolipoma, pheochromocytoma, and adrenocortical carcinoma. The characterization of an adrenal lesion is critical for an appropriate management of the patient, and is fundamentally based either on the functional or non functional behavior of the lesion, in addition to its benign or malignant nature. Functional adrenal lesions may be symptomatic, with typical clinical and laboratory features, like in many cases of cortical adenomas and pheochromocytomas, which makes their characterization easier. The characterization of non functional adrenal lesions represents a major diagnostic challenge. Extensive lesions may cause symptoms, while smaller lesions are in general incidentally identified or found during staging procedures in cancer patients. In both situations, the characterization of the lesion is strongly based on imaging diagnosis techniques. Fortunately, the advances achieved in the last years allow for a definition of the nature of most adrenal lesions. Computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine techniques, including positron emission tomography (PET), may be employed, and all of such techniques are clinically useful in the differentiation of such lesions. Stability is the simplest characteristic to be observed at imaging in order to define the nature of adrenal masses. The absence of growth determined by a simple analysis of previous images represents a consistent characteristic of benignity. The nature of an adrenal lesion is also related to its dimensions; lesions with < 4 cm in diameter tend to be benign, and those above 4 cm in diameter present higher risk for malignancy. CT and MRI techniques can also make the specific diagnosis of adenoma by taking advantage of the abundant amount of intracellular fat that is present in the majority of such lesions. In a pioneering study published in 1991, Lee et al. reported that the radiological attenuation at CT might effectively differentiate adrenal adenomas from non-adenomatous lesions. In a meta analysis, Boland et al. have demonstrated that, with a threshold of 10 Hounsfield units (HU), the test sensitivity for the diagnosis of adenoma would be 71%, and the specificity, 98%. In such a case,

Advanced imaging in COPD: insights into pulmonary pathophysiology.

Chronic obstructive pulmonary disease (COPD) involves a complex interaction of structural and functional abnormalities. The two have long been studied in isolation. However, advanced imaging techniques allow us to simultaneously assess pathological processes and their physiological consequences. This review gives a comprehensive account of the various advanced imaging modalities used to study COPD, including computed tomography (CT), magnetic resonance imaging (MRI), and the nuclear medicine techniques positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Some more recent developments in imaging technology, including micro-CT, synchrotron imaging, optical coherence tomography (OCT) and electrical impedance tomography (EIT), are also described. The authors identify the pathophysiological insights gained from these techniques, and speculate on the future role of advanced imaging in both clinical and research settings.

Consensus paper: radiological biomarkers of cerebellar diseases.

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.

Hyperpolarized 13C-Magnetic Resonance Spectroscopy

Myocardial metabolic abnormalities have been demonstrated widely in diverse cardiac diseases. Metabolic impairment may be secondary to the underlying pathophysiological mechanism; however, in most conditions, it could be considered a direct cause, or at least a cofactor, in the functional abnormalities of the heart. Article see p 895 A more complete understanding of the myocardial metabolic changes associated with cardiac diseases may lead to pharmacological studies and potentially new metabolic-targeted drugs. In heart failure, agents that act through the optimization of cardiac metabolism may be particularly attractive as they could potentially work without exerting negative hemodynamic effects; this would allow for their addition to current therapies.1 It has been demonstrated that shifting the metabolic substrate of the heart from fatty acids to carbohydrate oxidation can improve pump function and delay the progression of heart failure.2 That said, in spite of the initial enthusiasm over drugs that showed promising metabolic effects in vitro, few clinical benefits have been unequivocally demonstrated. A robust imaging technique, which would allow the direct assessment of metabolism in vivo, is essential to understanding the metabolic changes and the effectiveness of pharmacological drugs. Unfortunately, nuclear medicine techniques, such as positron emission tomography and single photon emission computed tomography, are unable to detect the metabolized tracers and distinguish between different downstream metabolites.3 Magnetic resonance spectroscopy (MRS) with hyperpolarized 13C-enriched substrates is a promising imaging technique for the evaluation of cardiac metabolism in vivo. Because the natural amount of 13C in biological tissue is low, a sufficient signal:noise ratio for 13C-MRS is obtained by increasing the polarization level (hyperpolarization) of these compounds. Currently, dynamic nuclear polarization is the most widely used hyperpolarization technique for 13C-enriched molecules and this enables an increased signal:noise ratio of ≈10 000-fold.4 13C-MRS allows for a …

Targeting Molecular Imaging Approach for Detection of Infection and Inflammation by Diagnostic Nuclear Medicine Techniques

Targeting Molecular Imaging Approach for Detection of Infection and Inflammation by Diagnostic Nuclear Medicine Techniques