Jiahe Tian

Does the Novel Integrated PET/MRI Offer the Same Diagnostic Performance as PET/CT for Oncological Indications?

Background We compared PET/MRI with PET/CT in terms of lesion detection and quantitative measurement to verify the feasibility of the novel integrated imaging modality for oncological applications. Methodology/Principal Findings In total, 285 patients referred to our PET/CT center for oncological indications voluntarily participated in this same-day PET/CT and PET/MRI comparative study. PET/CT images were acquired and reconstructed following routine protocols, and then PET/MRI was performed at a mean time interval of 28±11 min (range 15–45 min). PET/MRI covered the body trunk with a sequence combination of transverse T1WI 3D-volumetric interpolated breath-hold, T2WI turbo spin echo with fat saturation, diffusion-weighted imaging with double b values (50 and 800 s/mm2), and simultaneous PET acquisition over 45 min/5 bed positions. The maximum standardized uptake value (SUVmax) was assessed by manually drawn regions of interest over fluorodeoxyglucose-positive lesions. Among 285 cases, 57 showed no abnormalities, and 368 lesions (278 malignant, 68 benign and 22 undetermined) were detected in 228 patients. When stand-alone modalities were evaluated, PET revealed 31 and 12 lesions missed by CT and MRI, respectively, and CT and MRI revealed 38 and 61 more lesions, respectively, than PET. Compared to CT, MRI detected 40 more lesions and missed 8. In the integrated mode, PET/CT correctly detected 6 lesions misdiagnosed by PET/MRI, but was false-negative in 30 cases that were detected by PET/MRI. The overall diagnosis did not differ between integrated PET/MRI and PET/CT. SUVmax for lesions were slightly higher from PET/MRI than PET/CT but correlated well (ρ = 0.85–0.91). Conclusions/Significance The novel integrated PET/MRI performed comparatively to PET/CT in lesion detection and quantitative measurements. PET from either scanner modality offered almost the same information despite differences in hardware. Further study is needed to explore features of integrated PET/MRI not addressed in this study.

Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral μ-opioid receptor availability in rhesus monkeys.

Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real‐time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on μ‐opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95‐min positron emission tomography (PET) with 11C‐carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95‐min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low‐frequency TEAS efficacy.

Evaluation of nigrostriatal damage and its change over weeks in a rat model of Parkinson's disease: small animal positron emission tomography studies with [11C]β-CFT

INTRODUCTION The cardinal pathological feature of Parkinsons disease (PD) is progressive loss of dopaminergic neurons. Since dopamine transporter (DAT) is a protein located presynaptically on dopaminergic nerve terminals, radioligands that bind to these sites are promising radiopharmaceuticals for evaluation of the integrity of the dopamine system. This study using positron emission tomography (PET) tracers, [(11)C]-2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane ([(11)C]beta-CFT, radioligand for DAT), was aimed at evaluating the degree of nigrostriatal damage and its change over weeks in a rat model of PD. METHODS The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the medial forebrain bundle (MFB). Behavioral studies were carried out by apomorphine (APO) challenge prior to and 1, 2 and 4 weeks after MFB axotomy. Small animal PET scans were performed 2 days after the behavioral test. Immunohistochemistry was conducted 4 days after the last PET scan. RESULTS Compared with the contralateral intact side, a progressively decreased [(11)C]beta-CFT binding was observed on the lesioned side which correlated inversely with the APO-induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. CONCLUSION These findings not only demonstrate that the neuronal degeneration in this model is relatively slow, but also suggest [(11)C]beta-CFT is a sensitive marker to monitor the degree of nigrostriatal damage and its change over weeks. This marker can be used prospectively to study the progression of the disease, thereby making detection of early phases of PD possible.

An integrated quad-modality molecular imaging system for small animals.

We developed a novel integrated quad-modality system that included 3 molecular imaging methods (PET, SPECT, and fluorescence molecular imaging [FMI]) and 1 anatomic imaging modality (CT). This system could study various biologic processes in the same animal using multiple molecular tracers. In addition to the technology development, we also discussed the optimization strategy of the imaging protocols. The performance of this system was tested, and the in vivo animal experiment showed its power to trace 3 different molecular probes in living tissues. Our results demonstrated that this system has a great potential for the preclinical study of diseases. Methods: A prototype system integrating PET, SPECT, CT, and a charge-coupled device–based free-space FMI system has been developed. Imaging and fusion capabilities of the system were evaluated by a multimodality phantom. In addition, a mouse disease model with both tumor and inflammation was studied by this system to examine the in vivo performance. The 3 types of molecular probes—18F-FDG, [99mTc(HYNIC-3PRGD2)(tricine)(TPPTS)] (99mTc-3PRG2) (HYNIC = 6-hydrazinonicotinyl; TPPTS = trisodium triphenylphosphine-3,3′,3″-trisulfonate; 3PRGD2 = PEG4-E[PEG4-c(RGDfK)]2), and 3-(triethoxysilyl) propyl-Cy7–entrapped core-cross-linked polymeric micelle (Cy7-entrapped CCPM) nanoparticles—were used to target 3 different biologic processes in the tumor caused by pulmonary adenocarcinoma A549 cells. Moreover, the strategy to optimize multimodal molecular imaging procedure was studied as well, which could significantly reduce the total imaging time. Results: The imaging performance has been validated by both phantom and in vivo animal experiments. With this system and optimized imaging protocol, we successfully differentiated diseases that cannot be distinguished by a single molecular imaging modality. Conclusion: We developed a novel quad-modality molecular imaging system that integrated PET, SPECT, FMI, and CT imaging methods to obtain whole-body multimodality images of small animals. The imaging results demonstrated that this system provides more comprehensive information for preclinical biomedical research. With optimized imaging protocols, as well as novel molecular tracers, this quad-modality system can help in the study of the physiology mechanism at an unprecedented level.

Radionuclide imaging of mesenchymal stem cells transplanted into spinal cord

In vivo tracking of stem cells implanted to spinal cord by radionuclide imaging was investigated. The high expression of transferrin receptor on human mesenchymal stem cells (hMSCs) was verified by flow cytometry, radioligand binding and immunofluorescence. Radiolabelled transferrin was chosen as a tracer for scintigraphic imaging of the hMSCs transplanted into spinal cord of rabbits. Comparative experiments with radiolabelled human serum albumin as tracer and PBS as graft as well as ex vivo autoradiography demonstrated the specific uptake of radiolabelled transferrin of hMSCs. hMSCs could be detected in vivo with radiolabelled transferrin targeting at cellular transferrin receptors at an early stage after transplantation into spinal cord.

SUVmax/THKmax as a Biomarker for Distinguishing Advanced Gastric Carcinoma from Primary Gastric Lymphoma

Background Gastric carcinoma and primary gastric lymphoma (PGL) are the two most common malignancies in stomach. The purpose of this study was to screen and validate a biomarker of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for distinguishing advanced gastric carcinoma (AGC) from PGL for clinical applications. Methodology/Principal Findings We reviewed PET/CT scans collected from January 2008 to April 2012 of 69 AGC and 38 PGL (14 low-grade mucosa-associated lymphoid tissue [MALT], 24 non-MALT aggressive non-Hodgkin lymphoma [ANHL]) with a focus on FDG intensity (maximum standardized uptake value [SUVmax]) of primary lesions and its CT-detected abnormalities, including maximal gastrointestinal wall thickness (THKmax) and mucosal ulcerations. Gastric FDG uptake was found in 69 (100%) patients with AGC and 36 (95%, 12 MALT vs. 24 ANHL)with PGL. The presence of CT-detected abnormalities of AGC and PGL were 97% (67/69) and 89% (12 MALT vs. 22 ANHL), respectively. After controlling for THKmax, SUVmax was higher with ANHL than AGC (17.10±8.08 vs. 9.65±5.24, p<0.05) and MALT (6.20±3.60, p<0.05). THKmax did not differ among MALT, ANHL and AGC. Mucosal ulceration was more common with AGC (n = 9) than PGL (n = 2),but the difference was not statistically significant (p>0.05). Cross-validation analysis showed that for distinguishing ANHL from AGC, the classifier with SUVmax as a feature achieved a correct classification rate of 81% with thresholds 13.40±1.12 and the classifier with SUVmax/THKmax as a feature achieved a correct classification rate of 83% with thresholds 7.51±0.63. Conclusions/Significance SUVmax/THKmax may be as a promising biomarker of FDG-PET/CT for distinguishing ANHL from AGC. Structural CT abnormalities alone may not be reliable but can help with PET assessment of gastric malignancies. 18F-FDG PET/CT have potential for distinguishing AGC from PGL at the individual level.

Combination of dynamic 11C-PIB PET and structural MRI improves diagnosis of Alzheimer’s disease

Structural magnetic resonance imaging (sMRI) is an established technique for measuring brain atrophy, and dynamic positron emission tomography with (11)C-Pittsburgh compound B ((11)C-PIB PET) has the potential to provide both perfusion and amyloid deposition information. It remains unclear, however, how to better combine perfusion, amyloid deposition and morphological information extracted from dynamic (11)C-PIB PET and sMRI with the goal of improving the diagnosis of Alzheimers disease (AD) and mild cognitive impairment (MCI). We adopted a linear sparse support vector machine to build classifiers for distinguishing AD and MCI subjects from cognitively normal (CN) subjects based on different combinations of regional measures extracted from imaging data, including perfusion and amyloid deposition information extracted from early and late frames of (11)C-PIB separately, and gray matter volumetric information extracted from sMRI data. The experimental results demonstrated that the classifier built upon the combination of imaging measures extracted from early and late frames of (11)C-PIB as well as sMRI achieved the highest classification accuracy in both classification studies of AD (100%) and MCI (85%), indicating that multimodality information could aid in the diagnosis of AD and MCI.

Establish New Formulas for the Calculation of Renal Depth in Both Children and Adults.

Objective This study was performed to develop a new formula to estimate the renal depth in both children and adults; then compare the new formula with previously published formulas. Methods Renal depth and total thickness (T, cm) of the body at the level of the kidneys were measured by CT in 113 children and 246 adults. Their sex, age, height (H, cm), and weight (W, kg) were recorded. Multiple stepwise linear regression analysis were conducted, using data from children and adults together. The 359 cases were divided into 2 random groups, of which, the first group was used to derive a regressive formula, and the second was used to verify the formula and compare the formula with previously published formulas in different groups. Results Multiple stepwise linear regression analysis showed that the important variable in estimating the depth of each kidney was the ratio of body weight (W, kg) to body height (H, cm) and the total thickness (T, cm) of the body at the level of the kidneys. The new formula was as follows: for right renal depth (cm) = 0.22 × T + 7.714 × W/H-0.331 (r = 0.95), and for left renal depth (cm) = 0.238 × T + 6.553 × W/H-0.618 (r = 0.95). It is better than the other four formulas in different groups, especially in children and W/H ⩽ 0.30 (in adults) groups. Conclusions We first introduced T into renal depth estimation formula and established the new formula. It has a better performance than the other four formulas in different groups. The new formula provided reliable and accurate renal depth and may contribute to improving the methods used to estimate renal function from radionuclide renography.

Standardized uptake value based evaluation of lymphoma by FDG and FLT PET/CT

Although 18F‐FDG PET/CT imaging is the conventional method for evaluating lymphoma, PET/CT imaging with radiopharmaceuticals other than FDG is being investigated. We evaluated the utility of different standardized uptake value (SUV) measurements in 18F‐FLT PET/CT scans compared with PET/CT scans performed with FDG. Two scans, each using one of the radiopharmaceuticals, were performed on each of 114 patients with histologically proven lymphoma. Maximum and mean SUV (SUVmax) and (SUVmean) of all visualized lesions, with backgrounds of mediastinal blood pool, liver, spleen and vertebra were calculated. The ratios of the SUVs of the lesions to those of each reference region were statistically analyzed. Using receiver operating characteristic curves, we analyzed the differences in uptake of the two agents in aggressive and indolent B‐cell non‐Hodgkin lymphoma. We found that the SUVmax measurements of FDG were significantly different between aggressive and indolent B‐cell non‐Hodgkin lymphoma. The receiver operating characteristic curve of SUVmax of tumour/liver for FDG studies resulted in the most area under the curve. The SUVmax of the tumour/mediastinum ratio for FLT studies resulted in the most area under the curve (0.781). There was no significant correlation between FDG and FLT uptake in most types of lymphoma we studied. Further studies of the characteristics of 18F‐FLT should employ the tumour/mediastinum SUVmax ratio for accurate uptake measurement. Copyright

Evaluation of 18F-FDG and 18F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

In order to compare the efficacy of (18)F-fluorothymidine (FLT) and (18)F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P<0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P<0.001). Although increased apoptosis was observed in both cell lines after irradiation (P<0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β3, Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P<0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of (18)F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced (18)F-FDG uptake was only observed after 72 h. Therefore, we conclude that (18)F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells.