Emerging Role of Nuclear Medicine in Oral and Maxillofacial Surgery

During the past several years, nuclear medicine has emerged as one of the most useful imaging studies in oral and maxillofacial surgery, not only in diagnosis and staging but also in the management plan and follow-up protocols of many cancer or inflammatory diseases. Nuclear medicine has in addition a special place in treating several benign and malignant diseases. The practicing maxillofacial surgeon’s knowledge of nuclear medicine capabilities and advantages and disadvantages of each modality is crucial in his or her daily work. The purpose of this chapter is to clarify the important role of nuclear medicine in diagnosis and treatment of oral and maxillofacial region pathologies as well as its indications and limitations in the daily practice of the oral and maxillofacial surgeon

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

PURPOSE To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings

18F-fluoride PET/CT is highly effective for excluding metastases in patientes with equivocal bone scintigraphy

Orientador: Celso Darío RamosTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Finalidade: A cintilografia óssea (CO) tem sido amplamente utilizada por muitos anos para o diagnóstico de metástases ósseas, apesar da sua baixa especificidade e taxa significativa de lesões indeterminadas. PET/CT ósseo com fluoreto-18F tem comprovada alta sensibilidade e especificidade na detecção de lesões ósseas malignas, mas a sua eficácia em pacientes com lesões inconclusivas na CO não está bem documentada. Este estudo avaliou a capacidade do PET/CT com fluoreto-18F para excluir metástases ósseas em pacientes com diferentes tumores malignos primários e achados inespecíficos na CO. Métodos: Foram estudados 42 pacientes (34-88 anos de idade, 26 mulheres), com diferentes tipos de tumores. Todos os pacientes haviam realizado CO para estadiamento ou reestadiamento, a qual havia apresentado achados inconclusivos. Todos foram submetidos a PET/CT com fluoreto-18F. Todas as anormalidades identificadas nas imagens das COs foram comparadas visualmente com os achados das imagens de PET/CT. Resultados: Todas os 96 lesões inconclusivas encontradas nas COs dos 42 pacientes foram identificadas nas imagens de PET/CT. PET/CT com fluoreto-18F corretamente excluiu metástases ósseas em 23 pacientes (68 lesões). Dos 19 pacientes (28 lesões), classificados por PET/CT como metastáticos, 3 (5 lesões) foram classificados como livre de metástases ósseas no seguimento. A sensibilidade, a especificidade e os valores preditivos positivo e negativo das imagens PET/CT com fluoreto-18F foram, respectivamente, 100%, 88%, 84% e 100% para a identificação de pacientes portadores de metástases ósseas (análise por paciente) e 100%, 93%, 82% e 100% para a identificação das lesões metastáticas (análise por lesão). Conclusão: Diversos fatores que tornam a CO inconclusiva não afetam as imagens PET/CT com fluoreto-18F, as quais apresentam alta sensibilidade e elevado valor preditivo negativo para a exclusão de metástases ósseas em pacientes com achados inconclusivos na CO convencionalAbstract: Purpose: Bone scintigraphy (BS) has been used extensively for many years for the diagnosis of bone metastases despite its low specificity and significant rate of equivocal lesions. 18F-Fluoride PET/CT has been proven to have a high sensitivity and specificity in the detection of malignant bone lesions, but its effectiveness in patients with inconclusive lesions on BS is not well documented. This study evaluated the ability of 18F-fluoride PET/CT to exclude bone metastases in patients with various malignant primary tumours and nonspecific findings on BS. Methods: We prospectively studied 42 patients (34¿88 years of age, 26 women) with different types of tumours. All patients had BS performed for staging or restaging purposes but with inconclusive findings. All patients underwent 18F-fluoride PET/CT. All abnormalities identified on BS images were visually compared with their appearance on the PET/CT images. Results: All the 96 inconclusive lesions found on BS images of the 42 patients were identified on PET/CT images. 18F-Fluoride PET/CT correctly excluded bone metastases in 23 patients (68 lesions). Of 19 patients (28 lesions) classified by PET/CT as having metastases, 3 (5 lesions) were finally classified as free of bone metastases on follow-up. The sensitivity, specificity, and positive and negative predictive values of 18F-fluoride PET/CT were, respectively, 100 %, 88 %, 84 % and 100 % for the identification of patients with metastases (patient analysis) and 100 %, 93%, 82 % and 100 % for the identification of metastatic lesions (lesion analysis). Conclusion: The factors that make BS inconclusive do not affect 18F-fluoride PET/CT which shows a high sensitivity and negative predictive value for excluding bone metastases even in patients with inconclusive conventional BSDoutoradoClinica MedicaDoutor em Ciências09/51799-3/2010FAPES

Spectrum of metastatic and nonmetastatic skeletal findings with dual-phase 18F-FECH PET/CT in patients with biochemical relapse of prostate cancer

INTRODUCTION: The aim of this study was to evaluate the spectrum of skeletal findings on dual-phase fluorine-18-fluoroethylcholine (F-FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. MATERIALS AND METHODS: Three hundred F-FECH PET/CT scans were evaluated prospectively. The low-dose CT features of all cases were categorized as isodense, sclerotic, lytic or mixed lytic/sclerotic and maximum standardized uptake value (SUVmax) values were calculated. Findings on F-FECH PET/CT were correlated with Technetium-99m-methylene diphosphonate planar bone scans and serum prostate-specific antigen. RESULTS: Patient age range was 50-90 years (median 71 years) and prostate-specific antigen values were in the range 0.04-372 ng/ml (Roche Modular method). Seventy-two lesions were detected on F-FECH PET/CT in 45 patients, including 31 (43%) in the pelvis, 17 (23%) in the spine (cervical 3, thoracic 8 and lumbar spine 6) and 10 (13%) in the ribs. Evaluation of low-dose CT in combination with PET helped to characterize benign findings in 21 (29%) lesions. The SUVmax for all except one benign lesion ranged from 0.49 to 2.15. In 51 (71%) lesions because of metastatic disease, SUVmax was 0.6-11.6 for those classified as sclerotic on low-dose CT, 0.7-8.58 for lytic lesions, 1.1-7.65 for isodense lesions and 1.27-3.53 for mixed lytic/sclerotic lesions. Of the 56 F-FECH-avid lesions, 21 lesions showed avidity on bone scan [3 (23%) of the 13 isodense lesions, 14 (40%) of the 35 sclerotic lesions, 2 (50%) of the lytic lesions and 2 (50%) of the mixed sclerotic/lytic lesions]. CONCLUSION: F-FECH PET/CT identified bone lesions in 15% of patients with suspected prostate cancer relapse. SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions was observed above SUVmax of 2.5. Low-dose CT of PET/CT is a useful tool to aid characterization

Facial Reconstruction: A Systematic Review of Current Image Acquisition and Processing Techniques

Plastic and reconstructive surgery is based on a culmination of technological advances, diverse techniques, creative adaptations and strategic planning. 3D imaging is a modality that encompasses several of these criteria while encouraging the others. Imaging techniques used in facial imaging come in many different modalities and sub-modalities which is imperative for such a complex area of the body; there is a clear clinical need for hyper-specialized practice. However, with this complexity comes variability and thus there will always be an element of bias in the choices made for imaging techniques

12 Chapters on Nuclear Medicine

The development of nuclear medicine as a medical specialty has resulted in the large-scale application of its effective imaging methods in everyday practice as a primary method of diagnosis. The introduction of positron-emitting tracers (PET) has represented another fundamental leap forward in the ability of nuclear medicine to exert a profound impact on patient management, while the ability to produce radioisotopes of different elements initiated a variety of tracer studies in biology and medicine, facilitating enhanced interactions of nuclear medicine specialists and specialists in other disciplines. At present, nuclear medicine is an essential part of diagnosis of many diseases, particularly in cardiologic, nephrologic and oncologic applications and it is well-established in its therapeutic approaches, notably in the treatment of thyroid cancers. Data from official sources of different countries confirm that more than 10-15 percent of expenditures on clinical imaging studies are spent on nuclear medicine procedures

Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome : a consensus statement from the FD/MAS international consortium

Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients’ advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally

Prosthetic joint replacements in hips and knees: pilot study for the development of a single imaging test in patients with painful prosthetic joint replacements. 18 F-Fluoride PET-CT and conventional radionuclide bone scans

An increasing number of annual joint replacement operations are performed. Prosthetic infection and aseptic loosening is very important and distinguishing between them allows prompt and accurate treatment but there is no consensus on how best to image these patients. I also reviewed the role of CT in prosthetic joint imaging with a spectrum of usual pathologic conditions and CT patterns. This showed that CT plays a significant role in detecting and demonstrating complications of joint prosthesis surgery but it may not be sufficient in itself. CT can be combined, in hybrid imaging, such as SPECT-CT and PET-CT. I assessed the magnitude of the problem with a retrospective study of painful prosthetic joints in UHCW from symptom onset to diagnosis. This demonstrated significant delays in diagnosis and the need for streamlined and reduced imaging tests with some patients undertaking multiple non-imaging and imaging tests. I performed a systematic review of the role of 18 F-NaF showed that sodium fluoride positron emission tomography (18 F-NaF-PET) is a promising tool with high sensitivity and specificity in the assessment of joint replacements after the ninth post-surgical month. A further study confirmed the practicality of performing dynamic 18 F NaF PET-CT in detecting aseptic loosening of lower limb prostheses but future research trials with larger patient populations are required. Beam hardening artefacts occur in CT and hybrid imaging of metallic prosthetic joints. A series of physics experiments to evaluate and correct beam hardening artefacts was performed to alleviate the problem. Beam hardening artefacts from prostheses reduce image quality on 18 F PET-CT. The experiments included pre-filtering with Aluminium; dual-energy CT and mathematical algorithms with MATLAB® filtered back projection. The results showed no significant difference in artefact reduction between the different methods. The artefact-reduction techniques introduce other secondary artefacts with subsequent image quality reduction. Analysis of data from the prospective dynamic 18 F-NaF PET-CT trial showed inconsistent results due to data corruption and dynamic 18 F-NaF data loss but quantitative methods with Time-Activity Curves and trend line assessment of 99m Tc-MDP 3-phase bone scans was more accurate. The trial problems were identified and suggestions were made for a larger study with opt-in methods for patient recruitment and more involved use of allied healthcare staff for patient recruitment. I designed and obtained funding for a study to use a novel radiopharmaceutical agent -99m Tc-Tilmanocept (Lymphoseek® ) to assess periprosthetic membranes in vivo. Lymphoseek® binds to the mannose receptor on the cell surface of macrophages and multinucleated giant cells which are likely to reflect wear particle aseptic loosening. Further in vitro periprosthetic membranes tests will also be performed using immunochemistry. This study has not yet been performed but it is hoped that a negative Tilmanocept scan would reassuringly make a diagnosis of wear particle induced aseptic loosening unlikely

Molecular Imaging of Prostate Cancer

Chapter 1 addresses the introduction to the thesis and provides epidemiology, etiology, metastatic spread, current diagnostics and clinical need of new biomarker for risk stratification of prostate cancer. Chapter 2 provides a detailed analysis of the distribution pattern of the three most used choline tracers: 18F-methylcholine, 11C-choline, and 18F-ethylcholine in metabolically and anatomically disease-free patients. The ranges of SUVmax, SUVmean and standard deviations have been presented. Potential pitfalls in evaluation of “non-avid” but clinically significant presentation of different disease entities are also addressed. The chapter provides overview of the variations in choline uptake pattern which is vital for assessment of various organs when imaging is performed for evaluation of metastatic disease. Chapter 3 presents the feasibility of assessing dynamic 18F Ethyl Choline PET with a view to do kinetic modelling in clinical setting of biochemical relapse of Prostate Cancer. This critical piece of work underpins the quantification, tracer kinetics and demonstrates that cancerous tissue shows abnormal perfusion. From these observations I was able to conclude that 18F Choline can act as a biomarker to assess angiogenesis in prostate cancer and introduces 18F Choline as a biomarker for further work presented in chapter 4-8. Chapter 4 addresses the detection of clinically significant and insignificant prostate cancer on 18F-FECH PET/CT and I correlated findings with template guided prostate mapping biopsy (TPM). Sensitivity and Specificity data of 8F-FECH PET/CT has been provided. Chapter 5 addresses the accuracy of 18F Choline PET/MR which is compared to reference standard (template guided prostate mapping biopsy). This work suggests that data obtained from 18F Choline PET/MR can allow detection of clinically significant and insignificant prostate cancer. I noted that multiple previous treatments can give false positive results and 18F Choline PET/MR is the imaging investigation of choice post HIFU. Moreover, false negative results with 18F Choline PET/MR can be due to very small volume (=/<2 mm) disease. Chapter 6 presents the differential diagnosis of abnormal tracer accumulation in the Prostate and periprostatic tissue. Chapter 7 provides spectrum of skeletal findings on dual-phase 18F-fluoroethylcholine (FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. I have provided quantification data and explained that SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions also exists. Chapter 8 addresses the clinical utility of 18F Choline in the setting of clinical trial in collaboration with Uro-oncology, Nuclear Medicine and Radiology departments. This critical work compares 18F Choline PET-CT and Whole-Body MRI in assessment and decision-making process for salvage treatment of focal radio-recurrent prostate cancer. This chapters concludes that at present WB-MRI cannot be used alone as imaging modality for investigation of biochemical relapse of Prostate Cancer. Chapter 9 is a summary of main findings and discussions from chapters in this thesis. It also highlights the potential applications and future perspectives of novel biomarkers for imaging of prostate cancer