Annals of Nuclear Medicine (v.29, #3)

The role of molecular imaging in the evaluation of myocardial and peripheral angiogenesis by Mitchel R. Stacy; Jin Chul Paeng; Albert J. Sinusas (217-223).
Angiogenesis, or the formation of new microvasculature, is a physiological process that may occur in the setting of chronic tissue ischemia and can play an important role in improving tissue perfusion and blood flow following myocardial infarction or in the presence of peripheral vascular disease (PVD). Molecular imaging of angiogenesis within the cardiovascular system is a developing field of study. Targeted imaging of angiogenesis has the potential for non-invasive assessment of the underlying molecular signaling events associated with the angiogenic process and, when applied in conjunction with physiological perfusion imaging, may be utilized to predict and evaluate clinical outcomes in the setting of ischemic heart disease or PVD. This review discusses the developing radiotracer-based imaging techniques and technology currently in use that possess potential for clinical translation, with specific focus on PET and SPECT imaging of myocardial and peripheral angiogenesis.
Keywords: Myocardial angiogenesis; Peripheral angiogenesis; Molecular imaging; PET; SPECT

Comparison of 11C-4′-thiothymidine, 11C-methionine, and 18F-FDG PET/CT for the detection of active lesions of multiple myeloma by Momoko Okasaki; Kazuo Kubota; Ryogo Minamimoto; Yoko Miyata; Miyako Morooka; Kimiteru Ito; Kiichi Ishiwata; Jun Toyohara; Tomio Inoue; Risen Hirai; Shotaro Hagiwara; Akiyoshi Miwa (224-232).
The aims of this study were to evaluate the possibility of using 11C-methionine (11C-MET) and 11C-4′-thiothymidine (11C-4DST) whole-body PET/CT for the imaging of amino acid metabolism and DNA synthesis, respectively, when searching for bone marrow involvement in patients with multiple myeloma (MM) and to compare these findings with those for 18F-FDG PET/CT and aspiration cytology.A total of 64 patients with MM, solitary plasmacytoma, monoclonal gammopathy of undetermined significance, or an unspecified diagnosis were prospectively enrolled. All the patients underwent three whole-body PET/CT examinations within a period of 1 week. First, the tracer accumulation was visually evaluated as positive, equivocal, or negative for 55 focal lytic lesions visualized using CT in 24 patients. Second, the percentages of marrow plasma cells as calculated using a bone marrow aspiration smear and tracer accumulation were evaluated in the posterior iliac crests of 36 patients.Among the 55 lytic lesions, the 11C-MET and 11C-4DST findings tended to reveal more positive findings than the 18F-FDG findings. Based on the standard criteria for the diagnosis of active myeloma using the percentage of marrow plasma cells, significant differences were found between the 18F-FDG and 11C-MET findings and between the 18F-FDG and 11C-4DST findings, but no significant difference was observed between the 11C-MET and 11C-4DST findings.The addition of 11C-MET and 11C-4DST to 18F-FDG when performing PET/CT enabled clearer evaluations of equivocal lesions. Based on cytological diagnostic criteria, 11C-MET and 11C-4DST were more sensitive than 18F-FDG for the detection of active lesions. 11C-MET and 11C-4DST were more useful than 18F-FDG for the detection of active lesions, especially during the early stage of disease.
Keywords: FDG; Methionine; 11C-4′-thiothymidine; PET/CT; Multiple myeloma

Measurement of inter- and intra-observer variability in the routine clinical interpretation of brain 18-FDG PET-CT by Nicolas Brucher; Ramin Mandegaran; Thomas Filleron; Thomas Wagner (233-239).
To objectify and quantify inter- and intra-observer variability of brain 18-FDG PET-CT interpretation in the context of cognitive and functional impairment amongst the elderly.25 patients underwent brain 18-FDG PET-CT for investigation of dementia/MCI and frail elderly patients. Three observers interpreted studies in two forms: standardised datasets reconstructed by an outside observer and individualised reconstructions. Observers graded regional 18-FDG uptake in 11 brain areas and gave overall impressions on studies as pathological/normal. One observer repeated this process following a 3-month interval. The Kappa statistic was used to calculate inter- and intra-observer agreement on grading of regional 18-FDG uptake and overall impressions of studies as pathological/normal.Moderate inter-observer agreement was observed across standardised and individualised dataset reconstructions when 11 regional brain areas were compared cumulatively and overall impressions on studies were given as pathological vs normal. Higher levels of inter-observer agreement were found when comparing high versus low grading of regional uptake and when reporting standardised reconstructions. Intra-observer agreement between standardised vs individualised dataset reconstructions were moderate-to-fair across 11 brain regions cumulatively. Temporal intra-observer agreement of individualised dataset reconstructions comparing normal vs pathological opinions showed strong agreement (κ = 0.884 [95 % CI 0.662; 1.000)].Despite a strong agreement in final diagnosis, this study demonstrates a moderate inter- and substantial intra-observer reproducibility in reporting brain 18-FDG PET-CT. Such results suggest that the visual analysis approach is different between nuclear physicians but leads to the same final diagnosis.
Keywords: Brain FDG PET-CT; Inter-observer variability; Intra-observer variability; Dementia; Mild cognitive impairment

The evaluation of left ventricular dyssynchronization in patients with hypertension by phase analysis of myocardial perfusion-gated SPECT by Semra Ozdemir; Bahadır Kırılmaz; Ahmet Barutçu; Yusuf Ziya Tan; Fatmanur Çelik; Semra Akgoz (240-247).
Hypertension is one of the most important risk factors for cardiovascular disease. However, hypertension may also result in left ventricular dyssynchrony (LVD) which is characterized by delayed activation of certain ventricular segments leading to uncoordinated contraction. The aim of this study was to evaluate the LVD measured by phase analysis of gated single-photon emission computed tomography (SPECT) imaging in patients with hypertension.We retrospectively reviewed the records of the patients who have referred to our institution for myocardial perfusion imaging (MPI) with a diagnosis of cardiovascular disease. In this study, total of 196 patients (127 females and 69 males, with a mean age of 59.62 ± 10.27 years) with and without hypertension (123 and 73, respectively) were included. Phase analysis parameters were compared in patients with and without hypertension which are derived using Emory Cardiac Toolbox. Among these 196 patients, 72 had echocardiography results. The findings of echocardiographic and phase analysis were also compared. Student’s t test, Kruskal–Wallis, Mann–Whitney U test and Spearman correlation test were used to compare the results.There were statistically significant differences in the phase standard deviation (p = 0.005) and histogram bandwidth (p < 0.001) parameters of the phase analysis between the patients with and without hypertension groups, respectively. Furthermore, echocardiographic findings were significantly correlated with the result of the phase analysis.This study suggested that routine use of phase analysis-gated SPECT imaging will be beneficial for the diagnosis of LVD.
Keywords: Left ventricular function; Technetium-99 m; Gated SPECT

Optimization of attenuation and scatter corrections in sentinel lymph node scintigraphy using SPECT/CT systems by Hiroto Yoneyama; Hiroyuki Tsushima; Masahisa Onoguchi; Takahiro Konishi; Kenichi Nakajima; Shinro Matsuo; Daiki Kayano; Hiroshi Wakabayashi; Anri Inaki; Seigo Kinuya (248-255).
Although SPECT/CT systems have been used for sentinel lymph node (SLN) imaging, few studies have focused on optimization of attenuation correction (AC) and scatter correction (SC). While SLNs could be detected in conventional planar images, they sometimes do not appear in SPECT/CT images. The purpose of this study was to investigate the optimal AC and SC and to improve the detectability of SLNs in examinations using SPECT/CT systems.The study group consisted of 56 female patients with breast cancer. In SPECT/CT imaging, four kinds of images were created with and without AC and SC; namely, AC−SC−, AC+SC−, AC−SC+ and AC+SC+. Five nuclear medicine physicians interpreted the planar and SPECT/CT images with five grades of confidence levels (1–5). The detection rate was calculated as the number of patients whose average confidence levels of interpretation were more than 4, divided by the total number of patients.The confidence level of interpretation and the detection rate provided by the planar images were 4.76 ± 0.49 and 94.6 %, respectively. In SPECT/CT imaging, the AC+SC− provided the best detection rate (confidence level of interpretation, 4.81 ± 0.38; detection rate, 98.2 %), followed by the AC−SC− (4.70 ± 0.55, 89.3 %), and the AC−SC+ (4.39 ± 1.2, 78.6 %). The lowest values were obtained for the AC+SC+ (4.36 ± 1.22, 78.6 %). Regarding the confidence levels of interpretation, significant differences were observed between AC+SC− and AC−SC−, AC+SC− and AC+SC+, AC+SC− and AC−SC+, and between planar images and AC+SC+ (P = 0.0021, 0.0009, 0.0013, and 0.0056, respectively).When SPECT/CT was used, AC improved the detection of SLNs. SC caused disappearance of a faint SLN in some cases and should not be performed.
Keywords: SPECT/CT; Sentinel lymph node; Attenuation correction; Scatter correction; Breast cancer

Characteristics of images of angiographically proven normal coronary arteries acquired by adenosine-stress thallium-201 myocardial perfusion SPECT/CT-IQ⋅SPECT with CT attenuation correction changed stepwise by Teruyuki Takahashi; Haruki Tanaka; Nami Kozono; Yoshiki Tanakamaru; Naomi Idei; Norihiko Ohashi; Hideki Ohtsubo; Takenori Okada; Yuji Yasunobu; Shunichi Kaseda (256-267).
Although several studies have shown the diagnostic and prognostic value of CT-based attenuation correction (AC) of single photon emission computed tomography (SPECT) images for diagnosing coronary artery disease (CAD), this issue remains a matter of debate. To clarify the characteristics of CT-AC SPECT images that might potentially improve diagnostic performance, we analyzed images acquired using adenosine-stress thallium-201 myocardial perfusion SPECT/CT equipped with IQ⋅SPECT (SPECT/CT-IQ⋅SPECT) from patients with angiographically proven normal coronary arteries after changing the CT attenuation correction (CT-AC) in a stepwise manner.We enrolled 72 patients (Male 36, Female 36) with normal coronary arteries according to findings of invasive coronary angiography or CT-angiography within three months after a SPECT/CT study. Projection images were reconstructed at CT-AC values of (−), 40, 60, 80 and 100 % using a CT number conversion program according to our definition and analyzed using polar maps according to sex.CT attenuation corrected segments were located from the mid- and apical-inferior spread through the mid- and apical-septal regions and finally to the basal-anterior and basal- and mid-lateral regions in males, and from the mid-inferior region through the mid-septal and mid-anterior, and mid-lateral regions in females as the CT-AC values increased. Segments with maximal mean counts shifted from the apical-anterior to mid-anterolateral region under both stress and rest conditions in males, whereas such segments shifted from the apical-septal to the mid-anteroseptal region under both stress and rest conditions in females.We clarified which part of the myocardium and to which degree CT-AC affects it in adenosine-stress thallium-201 myocardial perfusion SPECT/CT-IQ⋅SPECT images by changing the CT-AC value stepwise. We also identified sex-specific shifts of segments with maximal mean counts that changed as CT-AC values increased.
Keywords: Myocardial perfusion imaging; Attenuation artifact; Computed tomography number conversion software

Monitoring of positron using high-energy gamma camera for proton therapy by Seiichi Yamamoto; Toshiyuki Toshito; Masataka Komori; Yuki Morishita; Satoshi Okumura; Mitsutaka Yamaguchi; Yuichi Saito; Naoki Kawachi; Shu Fujimaki (268-275).
In proton therapy, imaging of proton-induced positrons is a useful method to monitor the proton beam distribution after therapy. Usually, a positron emission tomography (PET) system installed in or near the proton beam treatment room is used for this purpose. However, a PET system is sometimes too large and expensive for this purpose. We developed a small field-of-view (FOV) gamma camera for high-energy gamma photons and used it for monitoring the proton-induced positron distribution.The gamma camera used 0.85 mm × 0.85 mm × 10 mm Ce:Gd3Al2Ga3O12 (GAGG) pixels arranged in 20 × 20 matrix to form a scintillator block, which was optically coupled to a 1-inch-square position-sensitive photomultiplier tube (PSPMT). The GAGG detector was encased in a 20-mm thick container and a pinhole collimator was mounted on its front. The gamma camera was set 1.2 m from the 35 cm × 35 cm × 5 cm plastic phantom in the proton therapy treatment room, and proton beams were irradiated to the phantom with two proton energies.The gamma camera had spatial resolution of ~6.7 cm and sensitivity of 3.2 × 10−7 at 1 m from the collimator surface. For both proton energies, positron distribution in the phantom could be imaged by the gamma camera with 10-min acquisition. The lengths of the range of protons measured from the images were almost identical to the simulation results.These results indicate that the developed high-energy gamma camera is useful for imaging positron distributions in proton therapy.
Keywords: Proton therapy; Positron; Gamma camera; Imaging

The aim of this study was to assess the range of normal adrenal FDG uptake, and to determine the diagnostic criteria of FDG PET-CT to differentiate adrenal nodule.A total of 117 healthy subjects who underwent FDG PET/CT for cancer screening, and 106 lung cancer patients who underwent FDG PET/CT for cancer staging without adrenal abnormality were enrolled to determine the normal range of adrenal standardized uptake value (SUV). In addition, another 24 lung cancer patients with suspicious adrenal masses were enrolled to evaluate the diagnostic performance of the different diagnostic criteria from FDG PET/CT.The adrenal maximal SUV (SUVmax) of the healthy group was 1.66 ± 0.21 in the right and 1.86 ± 0.30 in the left. The adrenal SUVmax of lung cancer group was 1.79 ± 0.30 in the right and 1.90 ± 0.37 in the left. Lung cancer group had a higher ratio of adrenal gland to liver (AL ratio) when compared with healthy subjects (0.77 ± 0.13 vs. 0.61 ± 0.10 on the right, 0.82 ± 0.12 vs. 0.68 ± 0.12 on the left: p < 0.001). The upper normal limits of adrenal SUVmax were calculated as the mean plus 2 standard deviations (right: 2.08 vs. 2.39, left: 2.46 vs. 2.64, in the normal group and lung cancer group, respectively). Using the upper limit from the lung cancer group, we achieved a sensitivity of 87 % and specificity of 100 %.We demonstrated that left adrenal gland had higher SUV than right adrenal gland both in healthy group and lung cancer group. Using the different normal range of bilateral adrenal SUVmax, we could successfully differentiate adrenal masses.
Keywords: Adrenal gland; Fluorodeoxyglucose (FDG); PET/CT; Lung cancer; Standardized uptake value (SUV)

Assessment of response to neoadjuvant radiochemotherapy with F-18 FLT and F-18 FDG PET/CT in patients with rectal cancer by Gundula Rendl; Lukas Rettenbacher; Johannes Holzmannhofer; Lidwina Datz; Cornelia Hauser-Kronberger; Gerd Fastner; Dietmar Öfner; Felix Sedlmayer; Christian Pirich (284-294).
The comparison of 2-deoxy-2-[18F]fluoro-d-glucose (F-18 FDG) and 3′-deoxy-3′-[18F]fluorothymidine (F-18 FLT) imaging in patients with rectal cancer before and after neoadjuvant radiochemotherapy (RCT) in relation to histopathology and immunohistochemistry obtained from surgery.20 consecutive patients (15 m, 5 f), mean age of 65 ± 10 years were included into this prospective study with a mean follow-up of 4.1 ± 0.8 years.Among histopathological responders (n = 8 out of 20), posttreatment F-18 FLT and F-18 FDG scans were negative in 75 % (n = 6) and 38 % (n = 3), respectively. The mean response index (RI) was 61.0 % ± 14.0 % for F-18 FLT and 58.7 % ± 14.6 % for F-18 FDG imaging. Peritumoral lymphocytic infiltration (CD3 positive cells) was significantly related to posttreatment SUVmax in F-18 FDG but not F-18 FLT studies.A significant decrease of SUVmax in F-18 FDG and F-18 FLT studies could be seen after RCT. Negative posttreatment F-18 FLT studies identified more histopathological responders.
Keywords: 18F-FDG; 18F-FLT; PET/CT; Rectal cancer; Radiochemotherapy

Clinical application of ultrasound for preparation of 99mTc-sestamibi complex by Alireza Doroudi; Mostafa Erfani; Behzad Norouzi; Seyyed Mostafa Saadati; Ali Kiasat; Faramarz Ahmadi; Behrooz Etesami; Mohammad Hadi Baghersad (295-301).
The main aim of this investigation is the clinical application of ultrasound irradiation technique as an alternative method to reconstitute sestamibi kits in comparison of water boiling bath method.The 740–3700 MBq (20–100 mCi) 99mTc-MIBI (sestamibi) complex samples were prepared due to ultrasound irradiation technique or boiled water bath method as a standard method. Twenty patients (8 men and 12 women; age range 30–72, median 52.45 years) have been referred to Golestan hospital for myocardial perfusion imaging (MPI). The subjects have been divided randomly into group A (3 men, 7 women, age range 36–67, median 51.7 years) and group B (5 men, 5 women, age range 30–72, median 50.3 years), respectively. The 99mTc-MIBI radiopharmaceuticals have been prepared by Ultrasound irradiation technique administrated to group A and 99mTc-MIBI complex samples due to the boiled water bath technique administrated to the other group. For all patients, the 2-day stress/rest MPI protocol was performed.The radio-HPLC and TLC studies have indicated that the 99mTc-MIBI complex samples with good yields could be prepared successfully due to new developed technique. The scintigraphy imaging studies have demonstrated that the 99mTc-sestamibi prepared due to the above-mentioned modalities shows very identical biodistribution in the heart, thyroid, lung, liver, gallbladder, kidneys, stomach, large intestine and bladder of the subjects. Any unexpected accumulation of radiotracer samples have not been observed in our approach.The ultrasound irradiation technique is convenient and sufficient method to prepare 99mTc-sestamibi. It can be recommended as an alternative method to reconstitute sestamibi kits particularly in emergency situations to reduce potentially medical risk by avoiding any delay in acute therapy for myocardial infarction.
Keywords: Sestamibi; 99mTc; 99mTc-MIBI; Ultrasound irradiation

Role of 18F-fluoride PET/CT over dual-phase bone scintigraphy in evaluation and management of lesions causing foot and ankle pain by Ji Young Kim; Yun Young Choi; Young Hwan Kim; Si-Bog Park; Mi Ae Jeong (302-312).
The purpose of this study was to assess the potential role of 18F-fluoride PET/CT over dual-phase bone scintigraphy (DBS) in evaluation and management of lesions causing foot and ankle pain. 99mTc-HDP DBS and 18F-fluoride PET/CT were performed in consecutive patients who visited rehabilitation department due to foot or ankle pain. Focal painful lesions in fore, mid, and hindfoot or ankle, and diffuse pain in foot were evaluated on DBS and 18F-fluoride PET/CT (conclusive, inconclusive, nonvisible) and lesions on each modality were correlated. The clinical course was followed to see if the results of 18F-fluoride PET/CT affected the decision of patient management.Sixty-one painful lesions in 31 patients included 16 forefoot (26.2 %), 11 midfoot (18.0 %), 19 hindfoot (31.2 %), 6 ankle (9.8 %), and 9 diffuse footpain (14.8 %). Forty lesions (40/61, 65.6 %) were detected on DBS, including 21 conclusive diagnostic (21/40, 52.5 %), mainly including hindfoot lesions (n = 11). The inconclusive 19 lesions (19/40, 47.5 %) on DBS showed conclusive diagnostic findings on 18F-fluoride PET/CT, mainly in fore and midfoot lesions (n = 15). Twenty-one painful lesions (21/61, 34.4 %) which were nonvisible on DBS revealed conclusive diagnostic findings on 18F-fluoride PET/CT in 7 lesions (7/21, 33.3 %), including 5 hindfoot lesions. Fourteen nonvisible lesions (14/21, 66.7 %) on both modalities included all 9 diffuse painful foot lesions. Patient management was affected by findings of 18F-fluoride PET/CT in 31 lesions (31/61, 50.8 %). 18F-fluoride PET/CT provided more confirmative diagnostic information in painful foot and ankle over DBS, and influenced patient management in many inconclusive or nonvisible cases on DBS. Increasing role of 18F-fluoride PET/CT in benign diseases including foot and ankle pain is expected in the near future.
Keywords: 18F-fluoride; PET/CT; Dual-phase bone scintigraphy; Foot pain; Spectrum of diseases; Diagnostic role; Clinical impact

Diagnostic efficacy of parametric clearance images in detection of renal scars in children with recurrent urinary tract infections by Jacek Kuśmierek; Ewa Pietrzak-Stelmasiak; Małgorzata Bieńkiewicz; Wojciech Woźnicki; Marian Surma; Izabela Frieske; Anna Płachcińska (313-318).
Static renal scintigraphy with Tc-99m dimercaptosuccinic acid (DMSA) is considered a scintigraphic gold standard in detection of post-inflammatory renal scars. Reports on usefulness of conventional summed (SUM) Tc-99 m mercaptoacetyltriglycine (MAG3) or Tc-99m ethylene dicysteine (EC) dynamic scintigraphic images in detection of renal scarring are ambiguous and some authors emphasize low sensitivity of this method. The work aimed at assessment of a diagnostic efficacy of parametric clearance images (PAR) generated from a dynamic renal scintigraphy in detection of renal scars.A study group consisting of 80 children (56 girls, 24 boys, age 5–18 years) with recurrent urinary tract infections (UTI) and documented one to five incidents of APN—28 children, and with recurrent UTI of the lower part of the urinary tract only—52 children. Altogether 160 kidneys were evaluated. Static renal Tc-99m DMSA SPECT scintigraphy and after 2–4 days Tc-99m EC dynamic renal scintigraphy were performed in every patient not earlier than 6 months after the last documented incident of UTI. PAR images generated from a dynamic renal scintigraphy acquired between 40 and 140 s. generated by in-house developed software and SUM images obtained in the same time period were compared with a reference Tc-99m DMSA SPECT study.For all kinds of images (SPECT, PAR and SUM), high indices of reproducibility were obtained—89 % (κ = 0.80), 88 % (κ = 0.78) and 89 % (κ = 0.73). Agreement in a Howard scale of a reference method (SPECT) with PAR and SUM methods amounted to 83 and 64 %, respectively (p = 0.004). Sensitivity and accuracy of PAR method as compared with SUM method were significantly higher: 89 vs. 49 % (p < 0.0001) and 88 vs. 73 % (p = 0.002), and specificity was slightly lower: 88 vs. 93 % (p = 0.043). SPECT and PAR methods revealed higher incidence of renal scars than a SUM method in patients with documented incident(s) of APN—64, 68 and 39 %, p = 0.009 and 0.008, respectively.PAR images generated from a dynamic renal scintigraphy improved sensitivity of detection of renal scars as compared with SUM images, providing a high reproducibility and diagnostic efficacy, similar to that of Tc-99m DMSA, in detection of post-inflammatory renal scarring.
Keywords: Chronic recurrent urinary tract infections; Renal scarring; Dynamic renal scintigraphy; Parametric renal clearance images