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Annals of Nuclear Medicine (v.24, #2)

Amyloid-plaque imaging in early and differential diagnosis of dementia by Alexander Drzezga (pp. 55-66).

The increasing life expectancy in our society results in a continuously growing number of patients suffering from neurodegenerative disorders, particularly Alzheimer’s disease (AD). Apart from the deleterious consequences for patients and their relatives, this issue has also alarming effects on our social systems. These facts have justified increased scientific efforts regarding the identification of basic pathomechanisms of dementia and the development of new treatment options. Increased production of specific proteins and their pathologic aggregation in the brain appears to be a pathomechanism which occurs early in the course of many different neurodegenerative diseases. Among the most well-known of these protein aggregations are amyloid plaques, which arise from the aggregation of the β-amyloid protein. Currently, this amyloid-aggregation pathology is regarded as a key pathology, playing a causal role in the development of AD. Consequently, modern therapy approaches are directed towards this target. Limited access to brain tissue has so far restricted the definite diagnosis of AD to postmortem histopathological assessment of brain tissue. For the same reason, a clear association between extent of amyloid deposition pathology and clinical course of AD has not been established so far. However, particularly with regard to new therapeutic options, a reliable in vivo diagnosis is required. Modern molecular imaging tracers such as [¹¹C]PIB do now open the possibility to visualize amyloid depositions in vivo, using positron emission tomography. This type of “in vivo histopathology” approach allows the characterization of neurodegenerative disorders on the basis of the underlying pathology rather than on their symptomatic appearance. In this manuscript, we will discuss the options of amyloid-plaque imaging regarding early and differential diagnosis of different forms of dementia as well as for patient selection for therapy trials and for objective therapy monitoring.

Keywords: Amyloid-plaque imaging; [¹¹C]PIB-PET; Alzheimer’s disease; Dementia; Neurodegeneration

The effect of giving detailed information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information by Eser Kaya; Ismail Ciftci; Reha Demirel; Yeliz Cigerci; Omer Gecici (pp. 67-76).

Nuclear medicine procedures use radiopharmaceuticals, which produce radiation and potential adverse reactions, albeit at a low rate. It is the patient’s ethical, legal, and medical right to be informed of the potential side effects of procedures applied to them. Our purpose was to determine the effect of providing information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information.This study was completed in two separate Nuclear Medicine Departments. The study included 620 (247 M, 373 F) patients who had been referred for myocardial perfusion, bone, dynamic renal, and thyroid scintigraphic examinations. The patients were divided into two groups according to whether they requested more information or not. Group 1 consisted of 388 patients who wanted to receive more information about the procedure, while Group 2 consisted of 232 patients who did not request additional information. The State-Trait Anxiety Inventory (STAI-S and STAI-T) was used to determine a patient’s anxiety level. After simple information was given, state and trait anxiety levels were measured in both groups. We gave detailed information to the patients in Group 1 and then measured state anxiety again. Detailed information included an explanation of the radiopharmaceutical risk and probable side effects due to the scan procedure.There was no statistical difference between Groups 1 and 2 in STAI-T or STAI-S scores after simple information was given (p = 0.741 and p = 0.945, respectively). The mean value of STAI-S score was increased after the provision of detailed information and there was a statistically significant difference between after simple information SATI-S and after detailed information STAI-S (p < 0.001). The STAI-S score was increased in 246 patients and decreased in 110 patients after detailed information, while there was no change in 32 patients. After detailed information, the greatest increase in STAI-S score was seen in the myocardial perfusion scan patients, when evaluating according to scan procedure (p < 0.001). However, in the dynamic renal patient group, there was no statistical difference (p = 0.271).Informed consent including detailed information about radiation exposure, the risk factors, and potential adverse reactions of intravenous radiopharmaceutical administration increased the patients’ anxiety level in those who request more information.

Keywords: Radiopharmaceuticals; Detailed information; Anxiety level

Additional value of integrated PET/CT over PET alone in the initial staging and follow up of head and neck malignancy by Tomohiro Ishikita; Noboru Oriuchi; Tetsuya Higuchi; Go Miyashita; Yukiko Arisaka; Bishnuhari Paudyal; Pramila Paudyal; Hirofumi Hanaoka; Mitsuyuki Miyakubo; Yoshiki Nakasone; Akihide Negishi; Satoshi Yokoo; Keigo Endo (pp. 77-82).

Clinical application of FDG-PET in head and neck cancer includes identification of metastases, unknown primary head and neck malignancy, or second primary carcinoma, and also recurrent tumor after treatment. In this study, the additional value of PET/CT fusion images over PET images alone was evaluated in patients with initial staging and follow up of head and neck malignancy.Forty patients with suspected primary head and neck malignancy and 129 patients with suspected relapse after treatment of head and neck malignancy were included. FDG-PET/CT study was performed after the intravenous administration of FDG (5 MBq/kg). Target of evaluation was set at primary tumor, cervical lymph node, and whole body. PET images and PET with CT fusion images were compared. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results of PET and PET/CT were compared with postoperative histopathological examination, and case by case comparison of PET and PET/CT results for each region was performed. The additional value of CT images over PET only images was assessed. Statistical differences in sensitivity and specificity were evaluated.In the comparative evaluation of 507 targets by PET alone and PET/CT, 401 targets showed agreement of the results. Of the 106 discordant targets, 103 showed a positive result on PET alone and negative result on PET/CT. These results showed a significant difference (p < 0.01). Sensitivity of PET/CT was slightly higher than that of PET without statistical significance, while specificity of PET/CT was significantly higher than that of PET alone (Initial staging: 90.5% vs. 62.2%, p < 0.01; Follow up: 97.2% vs. 74.4%, p < 0.01). In Fisher’s direct probability test, a significant difference was noted in the sensitivity (Initial staging: 91.3% vs. 87.0%, p < 0.01; Follow up: 93.9% vs. 91.4%, p < 0.01).Combined PET/CT showed improved diagnostic performance than PET alone by decreasing the number of false positive findings in patients with initial staging and follow up of head and neck malignancy.

Keywords: FDG-PET; PET/CT; Head and neck cancer; Staging; Diagnostic performance

No inhibitory effect on P-glycoprotein function at blood–brain barrier by clinical dose of clarithromycin: a human PET study with [¹¹C]verapamil by Ryosuke Arakawa; Hiroshi Ito; Masaki Okumura; Takuya Morimoto; Chie Seki; Hidehiko Takahashi; Akihiro Takano; Tetsuya Suhara (pp. 83-87).

To investigate the effects of the clinical dose of clarithromycin, a substrate of P-glycoprotein (P-gp), on P-gp function using positron emission tomography (PET) with [¹¹C]verapamil.Two PET scanning with [¹¹C]verapamil were performed before and after administration of 400 mg/day of clarithromycin on each of four healthy male subjects. The rate constant of transfer from plasma to brain (K ₁) was estimated by integration plot method. K ₁ values of [¹¹C]verapamil before administration of clarithromycin were 0.042–0.070 mL/cm³/min (0.054 ± 0.012) and those after administration were 0.037–0.066 mL/cm³/min (0.055 ± 0.013). No significant change in K ₁ values of [¹¹C]verapamil was observed between before and after administration of clarithromycin (P = 0.85). K ₁ values of [¹¹C]verapamil were not changed by clinical dose administration of clarithromycin, suggesting that a clinical dose of clarithromycin does not affect P-gp function at the blood–brain barrier.

Keywords: Blood–brain barrier; Clarithromycin; [¹¹C]Verapamil; P-glycoprotein; Positron emission tomography

Design and performance from an integrated PET/MRI system for small animals by Seiichi Yamamoto; Masao Imaizumi; Yasukazu Kanai; Mitsuaki Tatsumi; Masaaki Aoki; Eiji Sugiyama; Makoto Kawakami; Eku Shimosegawa; Jun Hatazawa (pp. 89-98).

Although simultaneous measurements of PET and magnetic resonance imaging (MRI) can provide interesting results in molecular imaging research, most of the combined systems are huge and animal handling in the system is not easy. To minimize these problems, we developed a compact integrated PET/MRI (iPET/MRI) system for small animals.For the iPET/MRI system, a new MR-compatible PET and a permanent magnet open MRI were designed. In the MRI, a tunnel is opened at the yoke of the magnet. The position-sensitive photo-multiplier tubes (PSPMTs) of the MR-compatible PET are positioned at the back of the yoke where the magnetic field is sufficiently low. The scintillators for the PET system are positioned at the center of the MRI magnets, and the direction of the scintillation photons is changed by slanted light guides, and they are fed to the PSPMTs by 75 cm long optical fiber bundles. The PET detectors employed two types of LGSO crystals (1.9 mm × 2.2 mm × 6 mm and 7 mm) with different decay times (33 and 43 ns) for depth of interaction detection. Sixteen optical fiber-based block detectors are arranged in a 112 mm diameter ring.The transaxial field-of-view (FOV) of the PET system is ~80 mm, and the axial FOV is 21 mm which can be enlarged by the axial motion of the PET detector ring during MRI acquisition. The transaxial and axial resolutions at the center of the PET system was 2.9 and 2.4 mm FWHM, respectively. The absolute sensitivity was 1.5% at the center of the axial FOV. Phantom images revealed no artifact in either the PET or MRI images. We successfully obtained simultaneously measured small animal images using the iPET/MRI system.The open geometry of the developed iPET/MRI facilitates easy accessibility to the subject. The iPET/MRI system appears to be a promising tool for molecular imaging research.

Keywords: PET; MRI; Simultaneous measurements; Small animal; Molecular imaging

The validity of multi-center common normal database for identifying myocardial ischemia: Japanese Society of Nuclear Medicine working group database by Kenichi Nakajima; Shinro Matsuo; Masaya Kawano; Naoya Matsumoto; Jun Hashimoto; Keiichiro Yoshinaga; Junichi Taki; Koichi Okuda (pp. 99-105).

The Japanese Society of Nuclear Medicine (JSNM) working group has created a myocardial perfusion imaging database applicable to standard acquisition protocol. The aim of this study is to validate the diagnostic accuracy of the common normal database compared with the expert interpretation of each institute.Five institutions participated in this study and used different acquisition settings which included 360°/180° rotation, camera configuration and camera orbits. The software and its version used in each institution also varied. The working group database was applied to detect the culprit coronary territory from a total of 166 patients with coronary artery disease (CAD) and 145 patients with low-likelihood of CAD.When summed stress score ≥4 was defined as significant abnormality, overall sensitivity, specificity and accuracy of patient-based analysis were 77, 72 and 75%, respectively, based on quantitative analysis using the common database, whereas those by institutional visual expert reading were 72, 79 and 75%, respectively.The common database, which was created by a multi-center working group and separated between male/female with 180/360° acquisitions, demonstrated comparable diagnostic accuracy to expert interpretation by each institute, and it may be applicable to multi-center studies.

Keywords: Myocardial perfusion imaging; Normal database; Japanese Society of Nuclear Medicine working group; Coronary artery disease; Quantification

How to manage RI venography in pre-orthopedic surgery patients by Kaori Terazawa; Hideki Otsuka; Yoichi Otomi; Naomi Morita; Shoichiro Takao; Seiji Iwamoto; Kyosuke Osaki; Masafumi Harada; Hiromu Nishitani (pp. 107-113).

The preoperative evaluation of venous thromboembolism (VTE) is important to avoid complications, because VTE is often induced by orthopedic surgery. We focused on radioisotope venography (RIV) using ^99mTc-macroaggregated human serum albumin, examining orthopedic patients.We conducted 34 examinations in 33 patients who were referred for RIV and lung perfusion scintigraphy for the pre-orthopedic operative evaluation of VTE. Two board-certified (one nuclear medicine board-certified) radiologists interpreted the images based on the following: (1) flow defect of the lower extremities; (2) interruption of flow; (3) irregular or asymmetric filling of the deep vein (low flow); (4) presence of collateral vessels; and (5) abnormal RI retention on delayed-phase images. Scoring was based on a 5-point scale, and more than 2 points was considered VTE positive.Abnormal findings were noted in 27 of the 34 examinations performed in the 33 patients and normal findings in the other 7 examinations. According to the RI score, 21 patients were classified into the VTE-positive group and 12 into the VTE-negative group. Surgery was canceled because of advanced age and respiratory dysfunction in 2 of the 21 patients in the VTE-positive group. Of the 19 patients who underwent surgery, an IVH filter was placed before surgery in 2 and anticoagulant treatment with heparin and warfarin was initiated on the day of surgery in 12 to prevent postoperative VTE, and only one of the patients receiving anticoagulant treatment developed PTE after surgery. Surgery was canceled due to advanced age and at patient’s request in 2 of 12 patients in the VTE-negative group. Anticoagulant treatment with heparin/warfarin was performed to prevent postoperative VTE in only 3 patients: one with a past medical history of pulmonary infarction, one with atrial fibrillation, and one suspected of having antiphospholipid antibody syndrome. No patient in the VTE-negative group developed VTE after surgery.The preoperative identification of patients with VTE by RIV might be useful for perioperative management and the evaluation of preventive measures against postoperative VTE.

Keywords: VTE; PTE; RIV; Orthopedic surgery

F-18 FDG PET/CT evaluation of radiotherapy response in rare case of mucosa-associated lymphoid tissue lymphoma by Ryogo Minamimoto; Ukihide Tateishi; Naoto Tomita; Yoshiaki Inayama; Motoko Omura-Minamisawa; Yoshibumi Tayama; Masaharu Hata; Yoshinobu Kubota; Tomio Inoue (pp. 115-119).

We experienced two cases of mucosa-associated lymphoid tissue (MALT) lymphoma arising at unusual locations and used F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to evaluate their response to radiation therapy (RT). A 62-year-old male with proven prostatic MALT lymphoma and a 43-year-old woman with proven duodenal MALT lymphoma had diffuse FDG uptake in the lesion. Both cases were treated with RT; following FDG, PET/CT showed decreased FDG uptake in each lesion. Neither patient had evidence of recurrence at more than 18 months after RT. FDG PET/CT is useful for indicating the treatment site in MALT lymphoma and in evaluation of therapeutic response following RT.

Keywords: Mucosa-associated lymphoid tissue (MALT) lymphoma; F-18 fluorodeoxyglucose (FDG); Positron emission tomography/computed tomography scan (PET/CT); Treatment response; Radiation therapy

Acknowledgments to reviewers (pp. 121-123).

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Annals of Nuclear Medicine (v.24, #2)