Ronald W. J. van Rheenen

Value of 11C-methionine PET in imaging brain tumours and metastases

Abstract11C-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduction provides a clinical overview of what is important in primary brain tumours, recurrent brain tumours and brain metastases. The indications for radiotherapy and the results and problems arising after chemoradiotherapy in relation to imaging (pseudoprogression or radionecrosis) are discussed. The working mechanism, scan interpretation and quantification possibilities of MET PET are then explained. A literature overview is given of the role of MET PET in primary gliomas (diagnostic accuracy, grading, prognosis, assessment of tumour extent, biopsy and radiotherapy planning), in brain metastases, and in the differentiation between tumour recurrence and radiation necrosis. Finally, MET PET is compared to other nuclear imaging possibilities in brain tumour imaging.

Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis

Abstract Objective: To assess the usefulness of bone scintigraphy with 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) for the detection of cardiac involvement in a group of patients with ATTR amyloidosis in different phases of disease, to relate the findings to echocardiography, ECG and cardiac biomarkers, and to evaluate different bone scintigraphic techniques and calculation methods for quantification of the cardiac uptake and for correlation with echocardiographic features and cardiac biomarkers. Methods: Forty-one patients underwent clinical examinations, echocardiography, ECG, measurement of cardiac biomarkers and bone scintigraphy (planar imaging and SPECT-CT) and were subsequently subdivided into three groups: (1) carriers of an amyloidogenic TTR mutation, n = 11, (2) proven ATTR amyloidosis without echocardiographically-defined (mean wall thickness >12 mm) cardiac amyloidosis (AC), n = 19, and (3) ATTR amyloidosis with echocardiographically-defined cardiac amyloidosis, n = 11. Planar and SPECT-CT images were analyzed visually according to a routine scoring system (grade 0–3) and semi-quantitatively by heart-to-whole body (H/WB) and heart-to-skull (H/S) ratio on planar images and by a left ventricle-blood pool ratio on SPECT-CT images. Results: All patients with ATTR and echocardiographically-defined AC and none of the carriers showed high cardiac uptake on bone scintigraphy. Furthermore, 8 out of 19 patients with ATTR without echocardiographically-defined AC showed high cardiac uptake. Highest correlations were found between H/S ratio on planar bone scintigraphy with troponin T (r = 0.76, p < 0.0001) and H/WB ratio with left ventricular mass index (r = 0.73, p < 0.0001). Conclusions: Bone scintigraphy with 99mTc-HDP may detect cardiac involvement in patients with ATTR amyloidosis prior to echocardiographic evidence of cardiac involvement. Cardiac uptake on bone scintigraphy correlates with severity of cardiac involvement using echocardiography, ECG and cardiac biomarkers. Visual grading and calculation of H/S ratio on planar imaging are the preferred methods to assess cardiac uptake.

The value of 11C-methionine PET in the differential diagnosis between brain tumor recurrence and radionecrosis

11C-methionine (MET) positron emission tomography (PET) is one of the most used nuclear imaging modalities in brain tumors. Because of its characteristics, MET-PET should be able to provide us a high detection rate of brain tumors and good lesion delineation. This book chapter provides a clinical overview of important issues in primary brain tumors, recurrent brain tumors, and brain metastases. The role and dilemmas in neuroimaging are discussed. The working mechanism, scan interpretation, and quantification possibilities of MET-PET are explained. An overview is given of the role of MET-PET in gliomas (diagnostic accuracy, grading, prognosis, and assessment of tumor extent) with special focus on available literature in the role of MET-PET to differentiate between tumor progression/recurrent tumor and radiation necrosis.

Additional diagnostic value of SPECT/CT to planar Iodine-123 labeled serum amyloid P component scintigraphy in a patient with pulmonary nodular amyloidosis

Localized pulmonary amyloidosis is a rare disease [1]. According to the Mayo Clinics experience, pulmonary amyloidosis can be divided into four types: tracheobronchial amyloidosis, nodular amyloidosis, infiltrating interstitial amyloidosis and lymph node amyloidosis [2]. The exact incidence of nodular pulmonary amyloidosis is not known; however, the amount of case reports and case series indicate that this diagnosis is well established [3,4]. In cases of nodular pulmonary amyloidosis and lymphocytic interstitial pneumonia, the presence of Sjögren’s disease should be considered [5,6]. Histopathological confirmation remains the gold standard for the diagnosis. The nodules appear heterogeneous on conventional chest X-ray images and contrast enhanced CT [7]. However, four types of CT findings are considered to be characteristic for the disease: sharp, lobulated contours; calcifications (in approximately half of the patients); varying size; and slowly progressive growth over years [8]. Despite these typical CT features, amyloidosis cannot be differentiated from granuloma, primary or spread neoplasms, or infection at the time of first presentation of such a patient. Nuclear medicine imaging techniques may provide additional information with regard to organ involvement, size and potential sites for biopsy to eventually acquire a definite diagnosis. Our group previously showed that Fluorine-18 labeled fluorodeoxyglucose positron emission tomography (F-FDG PET/CT) has potential to discriminate localized from systemic amyloidosis, and in addition may be an interesting tool for therapy evaluation [9,10]. However, F-FDG uptake in a lesion has a wide differential diagnosis, and is therefore non-specific for amyloidosis and should only be performed after amyloidosis has been diagnosed to further differentiate between localized and systemic types. In patients with nodular pulmonary amyloidosis, tracer accumulation on F-FDG PET/CT scans is frequently reported; however, this modality also lacks potential to discriminate [11]. Iodine-123 labeled serum amyloid P component (I-SAP) scintigraphy is the best validated nuclear medicine imaging modality to visualize specific organ involvement and therapy evaluation in amyloidosis [12]. For lung lesions, however, conventional planar I-SAP scintigraphy may be falsely negative, due to physiological blood pool accumulation in the mediastinum, relative high background activity in the lungs, and limited spatial resolution. Complementary single photon emission computed tomography combined with low-dose computed tomography (SPECT/CT) can be used to visualize in more detail smaller lesions in organs of interest and may therefore have additional diagnostic value in small lung lesions. In this report, we describe the additional use of I-SAP SPECT/CT for an identification of pulmonary involvement in localized amyloidosis, illustrated by a clinical case that turned out to have underlying Sjögren’s disease. Patient A is a 56-year-old woman who was referred to our amyloidosis referral center because of amyloid deposits in pulmonary tissue. Approximately six months before referral, she suffered from a persistent non-productive cough. Her general practitioner treated her for possible bronchitis, however without improvement. Conventional X-ray image of the thorax showed bilateral pulmonary consolidations, which was interpreted as metastases of an unknown primary malignancy. This assumption was further supported by contrast enhanced CT and F-FDG PET/CT scan (Figure 1). However, both modalities did not show a primary tumor. An open lung biopsy was performed and histological examination revealed lymphocytic interstitial pneumonia, with nodular AL amyloidosis accompanied by calcifications,

Clinical and 123I-SAP scintigraphy findings in three members from a family affected by AGel amyloidosis

The father, born in 1934, was 50 years old when AGel amyloidosis was detected in his eyes (cornea lattice dystrophy), a disease already known to be present in his father and aunt. Later, the mutation was characterized as D187N. He developed signs of cutis laxa later and needed facial surgery. He developed signs of polyneuropathy at 79 years and at that time, for the first time also, some loss of renal function (eGFR 50) was detected without proteinuria. His daughter, born in 1960, also had proven amyloid deposition and the same mutation. She only had some dryness of the eyes, facial weakness around the eyes and she had a normal renal function.

Perfusion SPECT: Its Role in the Diagnosis and Differential Diagnosis of Alzheimer’s Disease, with Particular Emphasis on Guidelines

Dementia is a clinical diagnosis reflecting many possible underlying pathologies, including, for example, vascular dementia and neurodegenerative disorders such as frontotemporal dementia, Lewy body-type disorder or Alzheimer’s disease (AD). The breakthrough of 99mtechnetium-labelled perfusion tracers in the 1990s resulted in many SPECT studies of flow changes in AD. In the first decade of 2000, the role of perfusion SPECT was shifted from diagnosis towards differential diagnosis, parallel to the growing attention for diagnosing early stages of dementia. This evolution is reflected in the upcoming guidelines, which are detailed in this chapter.

SPECT Imaging for Idiopatic M. Parkinson and Parkinsonian Syndromes: Guidelines and Comparison with PET and Recent Developments

According to the limited amount of literature available, there is no real difference in diagnostic accuracy between a DaT-SPECT scan and an 18F-FDOPA PET scan nor between an123I-IBZM SPECT and a 11C-raclopride PET. However, while DaT-SPECT and FDOPA PET have gained a role in the clinical evaluation of the parkinsonian patient, especially in the differential diagnosis with other pathologies such as essential tremor, less evidence has been presented for the use of IBZM SPECT in the differential diagnosis of Morbus Parkinson and parkinsonian syndromes. A promising role could be played by 18F-FDG PET or perfusion SPECT in this regard.

Cushingoid facies on 18

A variety of physiological artefacts can mimic pathology or even result in unreliable diagnostic images. An uncommon artefact can be seen in patients with glucocorticoid-induced Cushing syndrome. This 10-year-old girl, diagnosed with a mediastinal T-cell lymphoma, showed solitary mediastinal activity on baseline F-FDG PET (a). She was treated with chemotherapy and high doses of oral glucocorticoids, which eventually led to clinical signs of Cushing syndrome, including moon face and buffalo hump. Treatment of her disease was complicated by biopsy-proven cerebral fungal infection (aspergillosis) suggested on MRI. A second F-FDG PET/CT scan, performed to assess the extent of aspergillosis, showed increased heterogeneous regional uptake in the cutaneous tissues of the head, neck and shoulders (b) with normal findings on low-dose CT, and relatively reduced hepatic F-FDG uptake. This abnormal F-FDG distribution hampered correct scan reading and the scan was therefore decided not to be of diagnostic value for assessment of aspergillosis. This abnormal uptake pattern can be explained by glucocorticoid-induced promotion of the differentiation preadipocyte into mature adipocytes in central fatty tissue [1], which in turn have relatively high GLUT1 expression [2]. Reduced liver uptake can be due to prolonged use of glucocorticoids, inducing increased hepatic glucose output [3], resulting in increased “washout” of F-FDG. If changes in F-FDG uptake pattern due to high doses of glucocorticoids are seen, caution should be exercised in interpreting F-FDG PET scans because of possible artificial uptake reduction within regions of disease activity.

Cushingoid facies on 18 F-FDG PET/CT

A variety of physiological artefacts can mimic pathology or even result in unreliable diagnostic images. An uncommon artefact can be seen in patients with glucocorticoid-induced Cushing syndrome. This 10-year-old girl, diagnosed with a mediastinal T-cell lymphoma, showed solitary mediastinal activity on baseline F-FDG PET (a). She was treated with chemotherapy and high doses of oral glucocorticoids, which eventually led to clinical signs of Cushing syndrome, including moon face and buffalo hump. Treatment of her disease was complicated by biopsy-proven cerebral fungal infection (aspergillosis) suggested on MRI. A second F-FDG PET/CT scan, performed to assess the extent of aspergillosis, showed increased heterogeneous regional uptake in the cutaneous tissues of the head, neck and shoulders (b) with normal findings on low-dose CT, and relatively reduced hepatic F-FDG uptake. This abnormal F-FDG distribution hampered correct scan reading and the scan was therefore decided not to be of diagnostic value for assessment of aspergillosis. This abnormal uptake pattern can be explained by glucocorticoid-induced promotion of the differentiation preadipocyte into mature adipocytes in central fatty tissue [1], which in turn have relatively high GLUT1 expression [2]. Reduced liver uptake can be due to prolonged use of glucocorticoids, inducing increased hepatic glucose output [3], resulting in increased “washout” of F-FDG. If changes in F-FDG uptake pattern due to high doses of glucocorticoids are seen, caution should be exercised in interpreting F-FDG PET scans because of possible artificial uptake reduction within regions of disease activity.

Cushingoid facies on 18F-FDG PET/CT

A variety of physiological artefacts can mimic pathology or even result in unreliable diagnostic images. An uncommon artefact can be seen in patients with glucocorticoid-induced Cushing syndrome. This 10-year-old girl, diagnosed with a mediastinal T-cell lymphoma, showed solitary mediastinal activity on baseline F-FDG PET (a). She was treated with chemotherapy and high doses of oral glucocorticoids, which eventually led to clinical signs of Cushing syndrome, including moon face and buffalo hump. Treatment of her disease was complicated by biopsy-proven cerebral fungal infection (aspergillosis) suggested on MRI. A second F-FDG PET/CT scan, performed to assess the extent of aspergillosis, showed increased heterogeneous regional uptake in the cutaneous tissues of the head, neck and shoulders (b) with normal findings on low-dose CT, and relatively reduced hepatic F-FDG uptake. This abnormal F-FDG distribution hampered correct scan reading and the scan was therefore decided not to be of diagnostic value for assessment of aspergillosis. This abnormal uptake pattern can be explained by glucocorticoid-induced promotion of the differentiation preadipocyte into mature adipocytes in central fatty tissue [1], which in turn have relatively high GLUT1 expression [2]. Reduced liver uptake can be due to prolonged use of glucocorticoids, inducing increased hepatic glucose output [3], resulting in increased “washout” of F-FDG. If changes in F-FDG uptake pattern due to high doses of glucocorticoids are seen, caution should be exercised in interpreting F-FDG PET scans because of possible artificial uptake reduction within regions of disease activity.