Annals of Nuclear Medicine (v.23, #1)

Lung perfusion scintigraphy (LPS) with technetium-99m-labeled macro-aggregates of albumin (Tc-99m-MAA) is well established in the diagnostic of pulmonary embolism (PE). In the last decade, it was shown that single-photon emission computer tomography (SPECT) acquisition of LPS overcame static scintigraphy. Furthermore, there are rare indications for LPS, such as preoperative quantification of regional lung function prior to lung resection or transplantation, optimization of lung cancer radiation therapy, quantification of right-left shunt, planning of intra-arterial chemotherapy, and several rare indications in pediatrics. Moreover, LPS with Tc-99m-MAA is a safe method with low radiation exposure. PE can also be diagnosed by spiral computer tomography (CT), ultrasound, magnetic resonance angiography, or pulmonary angiography (PA, former gold standard). The present review considers all these methods, especially spiral CT, and compares them with LPS with respect to sensitivity and specificity and gives an overview of established and newer publications. It shows that LPS with Tc-99m-MAA represents a diagnostic method of continuing value for PE. In comparison with spiral CT and/or PA, LPS is not to be defeated as mentioned also by the most actual Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II reports. This applies in particular to chronic or recurring embolisms, whereas currently spiral CT may be of greater value for major or life-threatening embolisms. At present, LPS cannot be replaced by other methods in some applications, such as pediatrics or in the quantification of regional pulmonary function in a preoperative context or prior to radiation therapy. LPS still has a place in the diagnostics of PE and is irreplaceable in several rare indications as described earlier.
Keywords: Lung perfusion scintigraphy; Tc-99m-MAA; SPECT; Pulmonary embolism; Lung resection

Significant uptake of the thyroid is often identified as an incidental finding on whole-body F18-fluorodeoxyglucose positron emission tomography (FDG-PET) for non-thyroid disease. Sometimes, it is a dilemma for radiologists to interpret clinical significance of thyroid uptake and give adequate recommendation for further evaluation. In general, diffuse uptake of the thyroid glands on FDG-PET is considered to be benign and very likely secondary to thyroiditis and/or hypothyroidism; a further correlation or investigation of the thyroid function and/or ultrasound is helpful. Focal uptake of the thyroid on FDG-PET is defined as an incidentaloma, which is more clinically significant owing to its high risk of malignancy ranging 25–50%. Although maximum standardized uptake value and corresponding computed tomographic finding may help to differentiate benign from malignant lesion, a cytological diagnosis is often advised. The clinical significance of diffuse plus focal uptake of the thyroid on FDG-PET is not well known; it may also be associated with an increased risk of malignancy when compared with a diffuse uptake pattern only.
Keywords: FDG-PET; Thyroid; Incidentaloma; Thyroiditis

Comparison of Alzheimer’s disease with vascular dementia and non-dementia using specific voxel-based Z score maps by Shirou Ishii; Fumio Shishido; Masayuki Miyajima; Koutarou Sakuma; Takeshi Shigihara; Tadanobu Tameta; Makoto Miyazaki; Hiroshi Kuroda (25-31).
We investigated the ability to discriminate between Alzheimer’s disease (AD) and vascular dementia (VaD), and between AD and non-dementia using the program “easy Z score imaging system” (eZIS) developed by Matsuda et al., for the diagnosis of very early AD.Of 201 patients, we investigated 12 patients with AD, 10 with VaD, and 9 with non-dementia, who underwent brain perfusion single-photon emission computed tomography by technetium-99m ethyl cysteinate dimer (99mTc-ECD) between February 2005 and September 2006. The sensitivity and specificity of the indicators of specific volume of interest (VOI) analysis, namely, severity, extent, and ratio were evaluated for the distinction of AD from VaD and non-dementia.There was a significant difference in all the criteria for severity, extent, and ratio between AD and non-dementia cases and in the ratio between AD and VaD. Between AD and non-dementia, the sensitivity and specificity of severity were 100% and 45%, respectively, using the cutoff value of 1.19. When using the cutoff value of 14.2 for extent, the sensitivity and specificity were both 100%. Using the cutoff value of 2.22 for ratio, the sensitivity of 42% and specificity of 100% were demonstrated. When comparing AD with VaD, using the cutoff value of 2.22 for ratio, the sensitivity and specificity were 42% and 100%, respectively. Using the cutoff value of 1.5 for ratio, the sensitivity and specificity between AD and VaD were 92% and 80%, respectively, thereby showing the best results.The specific VOI analysis program of AD using specific voxel-based Z score maps is not influenced by interobserver differences among radiologists and is useful to discriminate AD from VaD and non-dementia. However, the setting of the cutoff value at each institution and comparison with original and eZIS images are suggested to distinguish better AD from VaD.
Keywords: Alzheimer’s disease; Vascular dementia; SPECT; Specific VOI analysis

An automated ROI setting method using NEUROSTAT on cerebral blood flow SPECT images by Toshiyuki Ogura; Kazuhiro Hida; Toshihide Masuzuka; Hisatoshi Saito; Satoshi Minoshima; Kazuhiro Nishikawa (33-41).
We have developed a method to automatically set regions of interest (ROI) (automated ROI) on cerebral blood flow single-photon emission computed tomography (SPECT) images with morphological information specific to the subjects. The objective was to set ROIs automatically without losing individual morphological information in the SPECT images and then evaluate its validity and clinical applicability.We constructed the volume of interest (VOI) template on the standardized brain generated by NEUROSTAT to determine the regions for ROIs to be set. Assuming patients with cerebral vascular disease, the VOI template was constructed so that the ROIs were drawn for the major vascular regions and 17 regions in total within the hemisphere, basal ganglia, thalamus, cerebellar cortex, cerebellar vermis, and pons. By comparing the major vascular occlusion models, the accuracy of region setting by the VOI template was evaluated for validation. Using the anatomical standardization of NEUROSTAT and inverse transformation, the automated ROI transformed the VOI template into the individual brain shape and then the VOI template was extracted from each slice to determine ROIs. An evaluation was made by visually investigating the effect of a different image quality and cerebral blood flow tracers using brain phantom and clinical data. The regional cerebral blood flow (rCBF), determined by the manual setting method of ROI (manual ROI) and automated ROI, was compared. We also compared automated ROI with other morphological images using clinical data.The VOI templates accurately showed the region with the reduced blood flow in the major vascular occlusion model, which validated the proper ROI setting. The brain phantom study demonstrated that ROI settings were least influenced by matrix size, image quality, and image rotation. The observation with the clinical data also indicated that the variation in cerebral blood flow tracers little affected the ROI settings. The comparison with manual ROI revealed a strong correlation between the two ROI settings, and the mean values within both ROIs were similar. The comparative evaluation with morphological images, obtained by magnetic resonance imaging (MRI), verified the accurate setting of ROI.The automated ROI achieved successful automatic ROI settings without distorting individual SPECT images. The automated ROI is not affected by the differences in the image quality or the cerebral blood flow tracers, which suggests versatile applicability. Thus, the use of automated ROI may eliminate the interoperator and interfacility variability in ROI setting and improve objectivity and reproducibility. It also allows comparative evaluation at the same transverse level with images acquired with other modalities such as MRI and is expected to enhance the clinical diagnosis.
Keywords: Cerebral blood flow SPECT; Automated ROI setting; NEUROSTAT; Inverse transformation; VOI template

Examination of pattern of RI accumulation in thyroid cartilage on bone scintigraphy by Hiroko Kurooka; Joji Kawabe; Chikako Tsumoto; Takehiro Hayashi; Ai Oe; Jin Kotani; Shigeaki Higashiyama; Etsushi Kawamura; Hideo Yamane; Susumu Shiomi (43-48).
In bone scintigraphy, abnormal RI accumulation in ossified thyroid cartilage is often noted. However, because similar accumulation is also seen in tumor-involved cartilage, distinction between these two lesions is sometimes difficult. We examined the differences in RI accumulation by ossification of the thyroid cartilage and cartilage invasion with anterior, posterior, and oblique views of bone scintigraphy in this study.This study included 120 patients (104 men, 16 women; mean age 67.8 ± 9.6 years; range 48–90 years) with laryngeal or lower pharyngeal carcinoma. The patients had exhibited abnormal accumulation of RI on thyroid cartilage on bone scintigraphy between February 1999 and March 2007. We evaluated accumulation of thyroid cartilage in the anterior, posterior, and oblique views on bone scintigraphy. The presence/absence of tumor invasion of the thyroid cartilage was checked by comparing the findings of enhanced computed tomography and magnetic resonance imaging (MRI) as well as evaluating operative records. RI accumulation in thyroid cartilage was divided into four types (diffuse accumulation, intense diffuse accumulation, slight inhomogeneous accumulation, and intense inhomogeneous accumulation).Tumor invasion of thyroid cartilage was noted in 2 of the 42 patients with diffuse accumulation, 1 of the 18 patients with intense diffuse accumulation, 1 of the 38 patients with slight inhomogeneous accumulation, and 17 of 22 patients with intense inhomogeneous accumulation. Because the degree of tumor invasion was highest in cases in which bone scintigraphy revealed intense inhomogeneous accumulation of RI in the thyroid cartilage, we judged this pattern of RI accumulation to be an indicator of tumor invasion. When diagnosis was based on this criterion, positive predictive value, negative predictive value, and accuracy were 77%, 96%, and 93%, respectively (P < 0.0001, Chi-square test).The findings of this study suggest that ossification of thyroid cartilage can be distinguished from tumor-involved thyroid cartilage on the basis of the pattern of abnormal RI accumulation in the thyroid cartilage in patients with head/neck cancer.
Keywords: Bone scintigraphy; Ossification of the thyroid cartilage; Cartilage invasion

Usefulness of FDG-PET/CT in the detection of pancreatic metastases from lung cancer by Motohiro Sato; Toshiyuki Okumura; Keiko Kaito; Moriyuki Kiyoshima; Yuji Asato; Keiko Uchiumi; Hiroaki Iijima; Ikuta Hashimoto; Takayuki Kaburagi; Ryuta Amemiya (49-57).
The objective of this study was to assess the ability to detect pancreatic metastasis of lung cancer and to clarify the degree of fluorodeoxyglucose (FDG) accumulation and computed tomography (CT) characteristics of pancreatic metastasis from lung cancer.A total of 573 patients (415 men and 158 women) with lung cancer were retrospectively evaluated. All patients underwent FDG-positron emission tomography (PET)/CT with contrast-enhanced CT for first=stage (313 patients; initial study group) or follow-up study (260 patients; follow-up study group). A lesion was regarded as positive for metastasis on the basis of visual judgment of the degree of increased metabolism by two experienced and independent interpreters, supported by semiquantitative evaluation on the basis of calculation of the maximum standardized uptake value (SUVmax).Abnormal accumulations in the pancreas were detected in 5 of 313 patients (1.60%) in the initial study group, and 6 of 260 patients (2.31%) in the follow-up study group. Seven of these patients had adenocarcinoma, three had small cell carcinoma, and the rest had large cell endocrine carcinoma. Tumor sizes (longitudinal diameter), measured by CT, of these 11 patients ranged from 6 mm to 52 mm (mean ± SD 8.3 mm ± 11.9 mm), and SUVmax for 1 h ranged from 3.37 to 11.1 (mean ± SD 6.12 ± 2.43). Three of these pancreatic lesions were difficult to determine by routine transaxial images, and detection was obvious only by thin-slice images or multiplanar reconstruction images. Contrast-enhanced CT showed gradual fill-in from the peripheral portion to the center. In addition, 10 of 11 cases did not show main pancreatic duct dilatation even if the tumor size was large.Metastases to the pancreas in lung cancer patients are not so rare and radiologists first have an important role to detect the pancreatic mass and then suggest to metastasis as the likely diagnosis. For this purpose, FDG-PET/CT has an advantage in depicting unsuspected pancreatic metastasis from lung cancer, particularly that which is not detected by CT alone.
Keywords: FDG; PET/CT; Lung cancer; Pancreas; Metastasis

It has been shown that [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can identify macrophage-rich high-risk atherosclerotic plaques in animal models as well as in patients with atherosclerotic plaques in the carotid arteries. The development of inflamed macrophage-rich plaques over time is not well known. This study was performed to determine the variability of such FDG-accumulating plaques between consecutive PET/CT examinations.Twenty-eight patients who underwent two whole-body FDG-PET/CT examinations within 7 months for malignant diseases were re-evaluated for atherosclerotic lesions in major arterial segments. The plaques were identified as active, inactive, or mixed depending on their appearance on PET and CT. Every identified plaque was compared with that of the other examination to evaluate the time-to-time correlation.The time-to-time correlation was close to 100% for calcified inactive plaques and about 50% for FDG-accumulating active plaques, with a high consistency between all examined arterial segments in this material.A large proportion of FDG-accumulating plaques can be identified on consecutive FDG-PET/CT examinations within 7 months.
Keywords: Nuclear medicine; 18F-FDG-PET/CT; Radiology; Atherosclerosis; Inflammation

Usefulness of a breath-holding acquisition method in PET/CT for pulmonary lesions by Toshiaki Yamaguchi; Osamu Ueda; Hideyuki Hara; Hiroto Sakai; Tohru Kida; Kayo Suzuki; Shuji Adachi; Kazunari Ishii (65-71).
To evaluate the usefulness of a breath-holding (BH) 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) technique for PET/computed tomography (CT) scanning of pulmonary lesions near the diaphragm, where image quality is influenced by respiratory motion.In a basic study, simulated breath-holding PET (sBH-PET) data were acquired by repeating image acquisition eight times with fixation of a phantom at 15 s/bed. Free-breathing PET (FB-PET) was simulated by acquiring data even as moving the phantom at 120 s/bed (sFB-PET). Images with total acquisition times of 15 s, 30 s, 45 s, 60 s, and 120 s were generated for sBHPET. Receiver-operating characteristic (ROC) analyses and determination of the statistical significance of differences between sFB-PET images and sBH-PET images were performed. A total of 22 pulmonary lesions in 21 patients (12 men and 9 women, mean age 61.3 ± 10.6 years, 10 benign lesions in 9 patients and 12 malignant lesions in 12 patients) were examined by FB-PET and BH-PET). For evaluation of these two acquisition methods, displacement of the lesion between CT and PET was considered to be a translation, and the statistical significance of differences in maximum standardized uptake value (SUVmax) of the lesion was assessed using the paired t test.In the basic study, sBH-PET images with acquisition times of 45 s, 60 s, and 120 s had significantly higher diagnostic accuracy than 120-s sFB-PET images (P < 0.05). In clinical cases, translation of the BH-PET images was significantly lower than that of the FB-PET images (benign: 5.29 ± 4.02 mm vs. 11.79 ± 8.27 mm, P = 0.005; malignant: 4.29 ± 3.36 mm vs. 18.26 ± 12.31 mm, P = 0.003). The SUVmax of the lesions in the BH-PET images was significantly higher than that in the FB-PET images (benign: 2.40 ± 0.86 vs. 2.20 ± 0.85, P = 0.005; malignant: 4.84 ± 2.16 vs. 3.75 ± 2.11, P = 0.001).BH-PET provides images with better diagnostic accuracy, avoids image degradation owing to respiratory motion, and yields more accurate attenuation correction. This method is very useful for overcoming the problem of respiratory motion.
Keywords: PET/CT; Free-breathing PET (FB-PET); Breath-holding PET (BH-PET); Translation; SUVmax

Integrated FDG-PET/CT compared with intravenous contrast-enhanced CT for evaluation of metastatic regional lymph nodes in patients with resectable early stage esophageal cancer by Masahiro Okada; Takamichi Murakami; Seishi Kumano; Masatomo Kuwabara; Taro Shimono; Makoto Hosono; Hitoshi Shiozaki (73-80).
To assess whether integrated fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can improve the diagnostic accuracy of metastatic regional lymph nodes (LNs) in esophageal cancer compared with contrast enhanced CT (CECT).We examined 180 consecutive patients with esophageal cancer by integrated PET/CT between April 2006 and March 2007. Eighteen patients (M:F 14:4) underwent radical esophagectomy after evaluations by PET/CT and CECT of 5–7-mm-thick slices 70–80 s after injection. Regional LNs of esophageal cancer were retrospectively reviewed on CECT images by two blinded evaluators on the basis of the following cutoff sizes: 7 mm for all regional LNs (Protocol A), 10 mm for paratracheal LNs (Protocol B), and 7 mm for others. In addition, the maximum standardized uptake value (SUVmax) on PET/CT was evaluated for positive uptake by LNs.Of 210 LNs excised at surgery, 25 were positive and 185 were negative for metastasis at pathology. The PET/CT images identified 15 true-positive and 184 truenegative LNs, whereas CECT identified 15 true positives and 176 true negatives in Protocol A, and 14 true positives and 180 true negative in Protocol B. The sensitivity, specificity, accuracy, positive, and negative predictive values of PET/CT were respectively 60.0%, 99.5%, 94.8%, 93.8%, and 94.8%, whereas those of CECT were 60.0%, 95.1%, 91.0%, 62.5%, and 94.6% (Protocol A) and 56.0%, 97.3%, 92.4%, 73.7%, and 94.2% (Protocol B). A comparison of the two CECT protocols revealed fewer false-positive LNs in Protocol B, but slightly lower sensitivity in Protocol B than in Protocol A. Substantial numbers of false-positive LNs were determined by CECT in the paratracheal regions (6 of 9, 66.7%) and CECT revealed central necrosis in 4 of 15 (26.7%) true-positive LNs > 1.8 cm. The mean SUVmax on PET/CT was 2.9 (range 1.7–5.5) in true-positive LNs. The smallest LN metastasis detectable by PET/CT was 6 mm.Integrated PET/CT improves the PPV of regional LNs when compared with CECT.
Keywords: Contrast-enhanced CT; FDG-PET/CT; Esophageal cancer; Metastatic lymph nodes

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study by Md. Mehedi Masud; Toshihiko Fujimoto; Masayasu Miyake; Shoichi Watanuki; Masatoshi Itoh; Manabu Tashiro (81-88).
Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using 18F-2-fluoro-2-deoxyglucose ([18F]FDG) and three-dimensional positron emission tomography (3-D PET).Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O2 consumption ( $$ dot V $$ O2max). [18F]FDG was injected 10 min later following the exercise task. Wholebody 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P < 0.05) were determined using Scheffe’s test (post hoc analysis).Quantitative analysis demonstrated that rMRGlc increased (P < 0.05) in the skeletal muscles of the thigh at mild or moderate workloads when compared with the resting controls. For visceral organs such as the liver and brain, metabolic reduction was significant (P < 0.05) at mild and/or moderate exercise workload.The present study demonstrated linear increases or decreases in glucose uptake by skeletal muscles and viscera with mild and moderate exercise workloads, suggesting the presence of homeostatic energy metabolism. This result supports the finding that [18F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% $$ dot V $$ O2max). The results of this investigation may contribute to sports medicine and rehabilitation science.
Keywords: 18F-2-fluoro-2-deoxyglucose ([18F]FDG); Positron emission tomography (PET); Exercise; Glucose metabolism; Regional metabolic rate of glucose (rMRGlc)

Evaluation of chemotherapy response in osteosarcoma with FDG-PET by Kenichiro Hamada; Yasuhiko Tomita; Atsuo Inoue; Tetsuho Fujimoto; Nobuyuki Hashimoto; Akira Myoui; Hideki Yoshikawa; Jun Hatazawa (89-95).
The objective of this study is to evaluate the utility of positron emission tomography (PET) with 2-deoxy-[18F] fl uoro-D-glucose (FDG) in the assessment of the chemotherapy response of osteosarcoma when compared with the degree of necrosis determined histologically.Whole-body FDG-PET scan was performed on 11 patients with osteosarcoma. All patients received neoadjuvant chemotherapy. The tumor size changes on magnetic resonance imaging; FDG-PET standardized uptake values prior to (SUV1) and following (SUV2) chemotherapy were analyzed and correlated with response to chemotherapy as assessed using histopathology in surgically excised tumors. Nine patients underwent FDG-PET scan both prior to and following neoadjuvant chemotherapy. The remaining two patients were examined only prior to surgery.Histologically, five patients had a good histologic response to chemotherapy (≧90% necrosis). The changes in tumor size did not correlate with histologic response (P > 0.05). SUV2 with good response was significantly lower than that with poor response (1.93 ± 0.50, 5.86 ± 2.55, respectively). Both the positive and negative predictive values of the SUV2 of less than 2.5 for a good response were 100%. Patients with good response showed a significantly higher ratio of SUV2 to SUV1 (SUV2:1) than patients with poor response (0.74 ± 0.11, 0.26 ± 0.39, respectively, P < 0.05). The positive and negative predictive values of SUV2:1 ≤ 0.5 for good and poor responses were 80% and 100%, respectively.FDG-PET imaging of osteosarcoma correlates positively with histologic response to neoadjuvant chemotherapy. SUV2 and SUV2:1 could be feasible as non-invasive surrogate predictors of response in osteosarcoma patients.
Keywords: Osteosarcoma; Positron emission tomography; Chemotherapy