Correlation Between Aquaporin 4 Expression and Different DWI Parameters in Grade I Meningioma

Purpose

Diffusion-weighted imaging (DWI) measures water diffusion in biological tissues. Cellular water transport depends on aquaporins (AQPs). The expression of aquaporins might differ in several pathologic disorders. Therefore, the aim of this study was to evaluate the associations between AQP4 expression and different DWI parameters in meningioma.

Procedures

Twenty-three patients with meningioma grade I were included in this retrospective study. DWI was obtained with three b values (0; 500; 1000) using a 1.5-T device. ADC_mean, ADC_min, ADC_max, and true diffusion coefficients (D) were obtained in every patient. Aquaporin 4 expression was quantified immunohistochemically in four immunoreactivity levels.

Results

The estimated DWI parameters (mean value ± standard deviation, 10^?3 mm² s^?1) of the tumors were as follows: ADC_min 0.67 ± 0.16, ADC_mean 0.94 ± 0.23, ADC_max 1.29 ± 0.50, and D 0.65 ± 0.23. The mean level of the AQP4 expression was 2.02 ± 0.75 points. A statistically significant correlation between AQP4 expression and ADC_max was identified (r = 0.508, p = 0.013). No significant correlations between AQP4 and other DWI parameters were found.

Conclusions

A clear correlation between AQP4 expression and ADC_max values in grade I meningioma was identified. There were no significant correlations between AQP4 expression and other DWI parameters, such as ADC_min, ADC_mean, and D.

     

18FDG-PET/MR观察宫颈鳞状细胞癌ADC值与SUV的相关性

目的 应用¹⁸FDG-PET/MR一体机观察宫颈鳞状细胞癌ADC值与FDG-PET标准化摄取值（SUV）的相关性。方法 对30例宫颈鳞状细胞癌患者行盆腔PET/MR检查。采用随机自带软件,利用轴位像对PET图像、ADC图及T2WI进行自动配准,并在同一层面勾画ROI,测量感兴趣体积（VOI）内肿瘤最大SUV（SUV_max）和平均SUV（SUV_mean）、最小ADC值（ADC_min）和平均ADC值（ADC_mean）。结果 30例宫颈鳞状细胞癌的ADC_min与SUV_max、ADC_min与SUV_mean、ADC_mean与SUV_max、ADC_mean与SUV_mean均无明显相关性;中-高分化和低分化宫颈鳞状细胞癌的上述ADC和SUV指标间亦无明显相关性。中-高分化与低分化宫颈鳞状细胞癌ADC_min差异有统计学意义（t=-2.06,P=0.049）。结论 ADC和SUV是诊断宫颈鳞状细胞癌的相互独立的指标。恶性程度分级评价中,ADC可能较SUV敏感。     

Response Monitoring with [<Superscript>18</Superscript>F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases

Purpose

The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3′-dexoy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.

Procedures

Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [¹⁸F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.

Results

5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [¹⁸F]FLT SUV_mean and SUV_max were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUV_max at days ?1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [¹⁸F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADC_mean) did not change in 5-FU-treated rats compared to untreated rats.

Conclusion

This study suggests that 5-FU treatment induces a flare in [¹⁸F]FLT uptake of responsive CC531 tumors in the liver, while the ADC_mean did not change significantly. Future studies in larger groups are warranted to further investigate whether [¹⁸F]FLT PET can discriminate between disease progression and treatment response.

     

Initial Experience with the Radiotracer Anti-1-amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) with PET in Renal Carcinoma

Purpose

Assessment of renal masses with conventional imaging may be challenging. Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) is a synthetic l-leucine analog with relatively little renal excretion. The present study examines anti-[¹⁸F]FACBC positron emission tomography uptake in patients with renal masses.

Procedures

Six patients with seven renal lesions were imaged dynamically for 2 h after injection of 10–10.9 mCi (370–403 MBq) anti-[¹⁸F]FACBC. Lesions were evaluated qualitatively and quantitatively and correlated with histology.

Results

Four clear cell and one Rosai–Dorfman lesion were hypo/isointense to normal cortex; two papillary lesions in the same patient were hyperintense. Mean SUV_max?±?SD at 30 min was 2.8?±?0.24 for clear cell carcinomas and 4.5?±?1.7 for papillary cell lesions. Mean SUV_max/SUV_mean ratios?±?SD of lesion to normal cortex at 30 min was 1.15?±?0.19 for the clear cell carcinomas and 2.3?±?0.84 for papillary cell.

Conclusions

In this small patient sample, relative amino acid transport compared with renal cortex is elevated in renal papillary cell carcinoma but not in clear cell carcinoma.     

一体化18F-FDG PET/MR评估缺血性脑血管病

目的 探讨一体化¹⁸F-FDG PET/MR显像对于慢性缺血性脑血管病的应用价值。方法 对10名成年健康志愿者及17例慢性单侧颈内动脉（ICA）或大脑中动脉（MCA）闭塞患者行一体化¹⁸F-FDG PET/MR检查。由2名医师分析图像，定量分析和比较健康志愿者左侧与右侧不同脑区、慢性缺血性脑血管病患者脑梗死患侧与对侧相应区域及脑梗死周围区与对侧相应区域间平均ADC值（ADC_mean）、平均标准化摄取值（SUV_mean）及最大标准化摄取值（SUV_max）的差异。结果 10名健康志愿者MRI均未见异常，¹⁸F-FDG脑代谢图像清晰，各脑区代谢分布对称；左侧与右侧额叶、顶叶、颞叶、枕叶ADC_mean、SUV_mean、SUV_max差异均无统计学意义（P均>0.05）。17例慢性缺血性脑血管病MRI均可见脑梗死灶，¹⁸F-FDG脑代谢图显示患侧均较对侧相应区域ADC_mean、SUV_mean、SUV_max明显减低（P均<0.01）；脑梗死周围区与对侧相应区域比较ADC_mean、SUV_mean、SUV_max亦明显减低（P均<0.01）。结论 利用一体化¹⁸F-FDG PET/MR检查可同时获得脑结构和脑代谢综合信息，全面评价慢性缺血性脑血管病。     

Positron Emission Tomography with [18F]-3′-Deoxy-3′fluorothymidine (FLT) as a Predictor of Outcome in Patients with Locally Advanced Resectable Rectal Cancer: a Pilot Study

Purpose

This pilot study was performed to evaluate whether tumor uptake of ¹⁸F-labeled 3′-deoxy-3′fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer.

Procedures

Fourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) and FLT before therapy and PET with FLT approximately 2 weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV_max). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS).

Results

Thirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV_max?≥?14.3), low during-therapy FLT uptake (SUV_max?<?2.2), and high percentage change in FLT uptake (≥60 %) were predictive of improved DFS (p?<?0.05 for all three values).

Conclusion

Pretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS.     

Uptake of Radium-223 Dichloride and Early [<Superscript>18</Superscript>F]NaF PET Response Are Driven by Baseline [<Superscript>18</Superscript>F]NaF Parameters: a Pilot Study in Castration-Resistant Prostate Cancer Patients

Purpose

The purpose of this study is to identify predictive factors on baseline [¹⁸F]NaF positron emission tomography (PET)/computed tomography (CT) of early response to radium-223 dichloride after 3 cycles of treatment in metastatic castration-resistant prostate cancer patients.

Procedures

Analysis of 152 metastases was performed in six consecutive patients who underwent [¹⁸F]NaF PET/CT at baseline and for early monitoring after 3 cycles of radium-223 dichloride. All metastases depicted on whole-body [¹⁸F]NaF PET/CT were contoured and CT (density in Hounsfield units, sclerotic, mixed, or lytic appearance) as well as [¹⁸F]NaF [maximum standardized uptake value (SUV_max), SUV_mean, and lesion volume (V_18F-NaF)] patterns were recorded. Tumor response was defined as percentage change in SUV_max and SUV_mean between baseline and post-treatment PET. Bone lesions were defined as stable, responsive, or progressive, according to thresholds derived from a recent multicentre test-retest study in [¹⁸F]NaF PET/CT. Total [¹⁸F]NaF uptake in metastases, defined as MATV × SUV_mean, was correlated to uptake of radium-223 on biodistribution scintigraphy performed 7 days after the first cycle of treatment.

Results

Among metastases, 116 involved the axial skeleton and 36 the appendicular skeleton. Lesions were sclerotic in 126 cases and mixed in 26 cases. No lytic lesion was depicted. ROC analysis showed that SUV_max and SUV_mean were better predictors of lesion response than V_18F-NaF and density on CT (P < 0.0001 and P = 0.001, respectively). SUV_max and SUV_mean were predictors of individual tumor response in separate multivariate models (P = 0.01 and P = 0.02, respectively). CT pattern (mixed versus sclerotic) and lesion density were independent predictors only when assessing response with delta SUV_max (P = 0.002 and 0.007, respectively). A good correlation between total [¹⁸F]NaF uptake within metastases and their relative radium-223 uptake assessed by two observers 7 days after treatment (r = 0.72 and 0.77, P < 0.0001) was found.

Conclusions

SUV_max and SUV_mean on baseline [¹⁸F]NaF PET/CT are independent predictors of bone lesions’ response to 3 cycles of radium-223 dichloride, supporting the use of NaF to select patients more likely to respond to treatment.

     

Independent prognostic value of whole-body metabolic tumor burden from FDG-PET in non-small cell lung cancer

Purpose

To determine whether whole-body metabolic tumor burden, measured as either metabolic tumor volume (MTV_WB) or total lesion glycolysis (TLG_WB), using FDG-PET/CT is an independent prognostic marker in non-small cell lung cancer (NSCLC).

Methods

328 patients with histologically proven NSCLC were identified for this retrospective analysis. This study was approved by our Institutional Review Board. All patients underwent baseline ¹⁸F-FDG-PET/CT scan imaging before therapy. The MTV_WB, TLG_WB, maximum standardized uptake value (SUV_maxWB) and mean standardized uptake value (SUV_meanWB) of tumors throughout the whole body were measured from FDG-PET images with semi-automated 3D contouring software.

Results

In univariate analysis, there was a statistically significant association of overall survival (OS) with the MTV_WB (hazard ratio (HR) = 1.62, p < 0.001), TLG_WB (HR = 1.47, p < 0.001). The patients with a MTV_WB ≤ median of 65.7 ml and TLG_WB ≤ median of 205.11 SUV_mean * ml had a median OS of 41.1 and 35.4 months compared with 9.5 and 9.7 months for those with a MTV_WB > 65.7 ml and TLG_WB > 205.11 SUV_mean * ml, respectively. From a series of multivariate Cox regression models, the MTV_WB and TLG_WB were significantly better than SUV_maxWB and SUV_meanWB at prognostication and significantly associated with patients’ OS with HRs of 1.50 (p < 0.001) and 1.42 (p < 0.001), respectively, after adjustment for patient’s age, gender and treatment intent as well as the tumor SUV_maxWB, histology and stage.

Conclusions

MTV_WB and TLG_WB as metabolic tumor burden measurements in ¹⁸F-FDG-PET/CT are independent prognostic markers and are significantly better than SUV_maxWB and SUV_meanWB at prognostication.     

Metabolic Tumor Burden Assessed by Dual Time Point [<Superscript>18</Superscript>F]FDG PET/CT in Locally Advanced Breast Cancer: Relation with Tumor Biology

Purpose

The aim of the study was to investigate the influence of dual time point 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) on the standard uptake value (SUV) and volume-based metabolic variables of breast lesions and their relation with biological characteristics and molecular phenotypes.

Procedures

Retrospective analysis including 67 patients with locally advanced breast cancer (LABC). All patients underwent a dual time point [¹⁸F]FDG PET/CT, 1 h (PET-1) and 3 h (PET-2) after [¹⁸F]FDG administration. Tumors were segmented following a three-dimensional methodology. Semiquantitative metabolic variables (SUV_max, SUV_mean, and SUV_peak) and volume-based variables (metabolic tumor volume, MTV, and total lesion glycolysis, TLG) were obtained. Biologic prognostic parameters, such as the hormone receptors status, p53, HER2 expression, proliferation rate (Ki-67), and grading were obtained. Molecular phenotypes and risk-classification [low: luminal A, intermediate: luminal B HER2 (?) or luminal B HER2 (+), and high: HER2 pure or triple negative] were established. Relations between clinical and biological variables with the metabolic parameters were studied. The relevance of each metabolic variable in the prediction of phenotype risk was assessed using a multivariate analysis.

Results

SUV-based variables and TLG obtained in the PET-1 and PET-2 showed high and significant correlations between them. MTV and SUV variables (SUV_max, SUV_mean, and SUV_peak) where only marginally correlated. Significant differences were found between mean SUV variables and TLG obtained in PET-1 and PET-2. High and significant associations were found between metabolic variables obtained in PET-1 and their homonymous in PET-2. Based on that, only relations of PET-1 variables with biological tumor characteristics were explored. SUV variables showed associations with hormone receptors status (p < 0.001 and p = 0.001 for estrogen and progesterone receptor, respectively) and risk-classification according to phenotype (SUV_max, p = 0.003; SUV_mean, p = 0.004; SUV_peak, p = 0.003). As to volume-based variables, only TLG showed association with hormone receptors status (estrogen, p < 0.001; progesterone, p = 0.031), risk-classification (p = 0.007), and grade (p = 0.036). Hormone receptor negative tumors, high-grade tumors, and high-risk phenotypes showed higher TLG values. No association was found between the metabolic variables and Ki-67, HER2, or p53 expression.

Conclusion

Statistical differences were found between mean SUV-based variables and TLG obtained in the dual time point PET/CT. Most of PET-derived parameters showed high association with molecular factors of breast cancer. However, dual time point PET/CT did not offer any added value to the single PET acquisition with respect to the relations with biological variables, based on PET-1 SUV, and volume-based variables were predictors of those obtained in PET-2.

     

[<Superscript>68</Superscript>Ga]PSMA-HBED-CC Uptake in Osteolytic,Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients

Purpose

The aim of this study was to evaluate potential differences in “Glu-NH-CO-NH-Lys” radio-labeled with [⁶⁸Ga]gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([⁶⁸Ga]PSMA-HBED-CC) uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate cancer (PC) patients.

Procedures

This retrospective study was approved by the local ethics committee. Patients who received [⁶⁸Ga]PSMA-HBED-CC positron emission tomography/computed tomography ([⁶⁸Ga]PSMA-PET/CT) with at least one positive bone metastasis were included in this study. Only patients who have not received systemic therapy for their PC were included. Bone metastases had to be confirmed by at least one other imaging modality or follow-up investigation. The maximum standardized uptake value (SUV_max) and mean Hounsfield units (HU_mean) of each metastasis were measured. Based on CT, each metastasis was classified as osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M).

Results

One hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of 154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154 (14.9%) as M, and 30/154 (19.5%) as BM. The SUV_max for the different types of metastases were 10.6 ± 7.07 (OB), 24.0 ± 19.3 (OL), 16.0 ± 21.0 (M), and 14.7 ± 9.9 (BM). The SUV_max of OB vs. OL and OB vs. BM metastases differed significantly (p ≤ 0.025). A significant negative correlation between HU_mean and SUV_max (r = ?0.23, p < 0.05) was measured.

Conclusions

[⁶⁸Ga]PSMA-HBED-CC uptake is higher in osteolytic and bone marrow metastases compared to osteoblastic metastases. Information derived from [⁶⁸Ga]PSMA-PET and CT complement each other for the reliable diagnosis of the different types of bone metastases in PC patients.

     

A Novel Framework for Automated Segmentation and Labeling of Homogeneous <Emphasis Type="Italic">Versus</Emphasis> Heterogeneous Lung Tumors in [<Superscript>18</Superscript>F]FDG-PET Imaging

Purpose

Determination of intra-tumor high-uptake area using 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) positron emission tomography (PET) imaging is an important consideration for dose painting in radiation treatment applications. The aim of our study was to develop a framework towards automated segmentation and labeling of homogeneous vs. heterogeneous tumors in clinical lung [¹⁸F]FDG-PET with the capability of intra-tumor high-uptake region delineation.

Procedures

We utilized and extended a fuzzy random walk PET tumor segmentation algorithm to delineate intra-tumor high-uptake areas. Tumor textural feature (TF) analysis was used to find a relationship between tumor type and TF values. Segmentation accuracy was evaluated quantitatively utilizing 70 clinical [¹⁸F]FDG-PET lung images of patients with a total of 150 solid tumors. For volumetric analysis, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) measures were extracted with respect to gold-standard manual segmentation. A multi-linear regression model was also proposed for automated tumor labeling based on TFs, including cross-validation analysis.

Results

Two-tailed t test analysis of TFs between homogeneous and heterogeneous tumors revealed significant statistical difference for size-zone variability (SZV), intensity variability (IV), zone percentage (ZP), proposed parameters II and III, entropy and tumor volume (p < 0.001), dissimilarity, high intensity emphasis (HIE), and SUV_min (p < 0.01). Lower statistical differences were observed for proposed parameter I (p = 0.02), and no significant differences were observed for SUV_max and SUV_mean. Furthermore, the Spearman rank analysis between visual tumor labeling and TF analysis depicted a significant correlation for SZV, IV, entropy, parameters II and III, and tumor volume (0.68 ≤ ρ ≤ 0.84) and moderate correlation for ZP, HIE, homogeneity, dissimilarity, parameter I, and SUV_min (0.22 ≤ ρ ≤ 0.52), while no correlations were observed for SUV_max and SUV_mean (ρ < 0.08). The multi-linear regression model for automated tumor labeling process resulted in R ² and RMSE values of 0.93 and 0.14, respectively (p < 0.001), and generated tumor labeling sensitivity and specificity of 0.93 and 0.89. With respect to baseline random walk segmentation, the results showed significant (p < 0.001) mean DSC, HD, and SUV_mean error improvements of 21.4 ± 11.5 %, 1.4 ± 0.8 mm, and 16.8 ± 8.1 % in homogeneous tumors and 7.4 ± 4.4 %, 1.5 ± 0.6 mm, and 7.9 ± 2.7 % in heterogeneous lesions. In addition, significant (p < 0.001) mean DSC, HD, and SUV_mean error improvements were observed for tumor sub-volume delineations, namely 5 ± 2 %, 1.5 ± 0.6 mm, and 7 ± 3 % for the proposed Fuzzy RW method compared to RW segmentation.

Conclusion

We proposed and demonstrated an automatic framework for significantly improved segmentation and labeling of homogeneous vs. heterogeneous tumors in lung [¹⁸F]FDG-PET images.

     

Hybrid FDG-PET/MR compared to FDG-PET/CT in adult lymphoma patients

Purpose

The goal of this study is to evaluate the diagnostic performance of simultaneous FDG-PET/MR including diffusion compared to FDG-PET/CT in patients with lymphoma.

Methods

Eighteen patients with a confirmed diagnosis of non-Hodgkin’s (NHL) or Hodgkin’s lymphoma (HL) underwent an IRB-approved, single-injection/dual-imaging protocol consisting of a clinical FDG-PET/CT and subsequent FDG-PET/MR scan. PET images from both modalities were reconstructed iteratively. Attenuation correction was performed using low-dose CT data for PET/CT and Dixon-MR sequences for PET/MR. Diffusion-weighted imaging was performed. SUV_max was measured and compared between modalities and the apparent diffusion coefficient (ADC) using ROI analysis by an experienced radiologist using OsiriX. Strength of correlation between variables was measured using the Pearson correlation coefficient (r _p).

Results

Of the 18 patients included in this study, 5 had HL and 13 had NHL. The median age was 51 ± 14.8 years. Sixty-five FDG-avid lesions were identified. All FDG-avid lesions were visible with comparable contrast, and therefore initial and follow-up staging was identical between both examinations. SUV_max from FDG-PET/MR [(mean ± sem) (21.3 ± 2.07)] vs. FDG-PET/CT (mean 23.2 ± 2.8) demonstrated a strongly positive correlation [r _s = 0.95 (0.94, 0.99); p < 0.0001]. There was no correlation found between ADC_min and SUV_max from FDG-PET/MR [r = 0.17(?0.07, 0.66); p = 0.09].

Conclusion

FDG-PET/MR offers an equivalent whole-body staging examination as compared with PET/CT with an improved radiation safety profile in lymphoma patients. Correlation of ADC to SUV_max was weak, understating their lack of equivalence, but not undermining their potential synergy and differing importance.

     

[<Superscript>18</Superscript>F]Fluorocholine Uptake of Parathyroid Adenoma Is Correlated with Parathyroid Hormone Level

Purpose

The aim of the study was to investigate the relationship between [¹⁸F]fluoromethyl-dimethyl-2-hydroxyethylammonium ([¹⁸F]FCh) positron emission tomography (PET) parameters, laboratory parameters, and postoperative histopathological results in patients with primary hyperparathyroidism (pHPT) due to parathyroid adenomas.

Procedures

This retrospective study was conducted in 52 patients with biochemically proven pHPT. [¹⁸F]FCh-PET parameters (maximum standardized uptake value: SUV_max) in early phase (after 2 min) and late phase (after 50 min), metabolic volume, and adenoma-to-background ratio (ABR), preoperative laboratory results (PTH and serum calcium concentration), and postoperative histopathology (location, size, volume, and weight of adenoma) were assessed. Relationship of PET parameters, laboratory parameters, and histopathological parameters was assessed using the Mann-Whitney U test and Spearman correlation coefficient. MRI characteristics of parathyroid adenomas were also analyzed.

Results

The majority of patients underwent a PET/MR scan, 42 patients (80.7 %); 10 patients (19.3 %) underwent PET/CT. We found a strong positive correlation between late-phase SUV_max and preoperative PTH level (r?=?0.768, p?<?0.001) and between late-phase ABR and preoperative PTH level (r?=?0.680, p?<?0.001). The surgical specimen volume was positively correlated with the PET/MR lesion volume (r?=?0.659, p?<?0.001). No significant association was observed between other [¹⁸F]FCh-PET parameters, laboratory parameters, and histopathological findings. Cystic adenomas were larger than non-cystic adenomas (p?=?0.048).

Conclusions

[¹⁸F]FCh uptake of parathyroid adenomas is strongly correlated with preoperative PTH serum concentration. Therefore, the preoperative PTH level might potentially be able to predict success of [¹⁸F]FCh-PET imaging in hyperparathyroidism, with higher lesion-to-background ratios being expected in patients with high PTH. PET/MR is accurate in estimating the volume of parathyroid adenomas.

     

Pilot Study of the Utility of the Synthetic PET Amino-Acid Radiotracer Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid for the Noninvasive Imaging of Pulmonary Lesions

Purpose

Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-3-[¹⁸F]FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in detection of prostate carcinoma and brain tumors and has also been shown to have uptake in lung tumor cell lines. The purpose of this study is to determine the uptake characteristics of anti-3-[¹⁸F]FACBC in lung carcinoma and if this radiotracer may help characterize pulmonary lesions.

Procedures

Ten patients with pulmonary lesions scheduled for surgical resection or biopsy underwent 45-min dynamic PET-CT imaging of the thorax after IV injection of 214.6–384.8MBq of anti-3-[¹⁸F]FACBC. Anti-3-[¹⁸F]FACBC uptake was compared with that of routine 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) PET-CT scans of the same patient and validated with a combination of pathology, imaging and clinical follow-up. Immunohistochemistry for Ki-67 was performed on tissue samples.

Results

There were nine malignant (seven lung nodules and two mediastinal nodes), two inflammatory, and one carcinoid lesion ranging from 1 to 3.75 cm. Mean(±SD) SUV_max of malignant lesions was 6.2(±2.6), 5.9(±2.7), 5.9(±3.4), and 5.7(±3.3), at 8, 16, 28, and 40 min, respectively; while for inflammatory lesions at the same time points, 4.1(±0.6), 3.3(±0.9), 2.2(±0.03), and 2.3(±0.03), respectively. The carcinoid tumor had SUV_max of 2.8, 2.6, 1.5, and 0.9 at similar time points. Mean SUV_max of all malignant lesions was higher than that of inflammatory lesions for anti-3-[¹⁸F]FACBC, and was statistically significant at greater than 28 min post-radiotracer infusion (p?<?0.05). There was no significant correlation of anti-3-[¹⁸F]FACBC activity with Ki67, though there was a positive trend. There was a strong correlation between anti-3-[¹⁸F]FACBC and [¹⁸F]FDG uptake.

Conclusions

Anti-3-[¹⁸F]FACBC uptake in malignant lesions is greater than in inflammatory lesions with a higher degree of separation of uptake on delayed imaging. More comprehensive study is required to determine the diagnostic performance of anti-3-[¹⁸F]FACBC in the characterization of pulmonary lesions.     

Early diffusion-weighted magnetic resonance imaging in children after cardiac arrest may provide valuable prognostic information on clinical outcome

Objective

We examined whether early diffusion-weighted magnetic resonance imaging (DW-MRI) abnormalities of the brain and variation of apparent diffusion coefficient (ADC) values can provide prognostic information on clinical outcome in children following cardiac arrest (CA).

Design

Retrospective study.

Setting

A 12-bed paediatric intensive care unit (PICU).

Patients

Children aged between 1 month and 18 years who had DW-MRI with ADC measurement within the first week following CA. Neurological outcomes were assessed using the Pediatric Cerebral Performance Category Scale (PCPC). Differences between the favourable (PCPC ≤3) and unfavourable (PCPC ≥4) groups were analysed with regard to clinical data, electrophysiological patterns as well as qualitative and quantitative DW-MRI abnormalities.

Results

Twenty children with a median age of 20 months (1.5–185) and a male/female sex ratio of 1.5 underwent DW-MRI after CA with a median delay of 3 days (1–7). Aetiologies of CA were (i) asphyxia (n = 10), (ii) haemodynamic (n = 5) or (iii) unknown (n = 5). With regard to DW-MRI findings, the unfavourable outcome group (n = 8) was associated with cerebral cortex (p = 0.02) and basal ganglia (p = 0.005) lesions, with a larger number of injured brain regions (p = 0.001) and a global decrease in measured ADC signal (p = 0.008). Normal DW-MRI (n = 5) was exclusively associated with the favourable outcome group (n = 12).

Conclusion

Qualitative, topographic and quantitative analysis of early DW-MRI with ADC measurement in children following CA may provide valuable prognostic information on neurological outcomes.     

[68Ga]-Albumin-PET in the Monitoring of Left Ventricular Function in Murine Models of Ischemic and Dilated Cardiomyopathy: Comparison with Cardiac MRI

Purpose

The purpose of this study is to evaluate left ventricular functional parameters in healthy mice and in different murine models of cardiomyopathy with the novel blood pool (BP) positron emission tomography (PET) tracer [⁶⁸Ga]-albumin.

Procedures

ECG-gated microPET examinations were obtained in healthy mice, and mice with dilative (DCM) and ischemic cardiomyopathy (ICM) using the novel BP tracer [⁶⁸Ga]-albumin (Alb_BP), as well as [¹⁸F]-FDG microPET. Cine-magnetic resonance imaging (MRI) examination performed on a clinical 1.5-T MRI provided the reference standard measurements.

Results

When considering the combined group of healthy controls, DCM and ICM Alb_BP-PET significantly overestimated the magnitudes of EDV (Alb_BP, 181?±?86 μl; cine-MRI, 125?±?80 μl; P?<?0.001) and ESV (Alb_BP, 136?±?92 μl; cine-MRI, 96?±?77 μl; P?<?0.001), whereas the EF (Alb_BP, 31?±?16 %; cine-MRI, 33?±?21 %; P?=?0.910) matched closely to cine-MRI results, as did findings with [¹⁸F]-FDG. High correlations were found between the measured cardiac parameters (EDV: R?=?0.978, ESV: R?=?0.989, and LVEF: R?=?0.992).

Conclusions

Measuring left ventricular function in mice with [⁶⁸Ga]-albumin BP PET is feasible and showed a high correlation compared to cine-MRI, which was used as a reference standard.     

Dynamic Changes of FDG Uptake and Clearance in Normal Tissues

Purpose

This study aims to evaluate dynamic 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) uptake in normal tissues.

Procedures

Thirty male patients underwent FDG positron emission tomography (PET)/computed tomography imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUV) were obtained in regions of interest of normal tissues.

Results

The aorta (blood pool), liver, and spleen FDG activity demonstrated significantly and continuously decreased activity from 1 to 2 and 2 to 3 h, while FDG uptake in the lungs, pancreas, lymph nodes, and skeletal muscle decreased from 1 to 2 h only. In contrast, the left ventricular myocardium demonstrated two patterns of dynamic changes: myocardium with higher FDG uptake (SUV_max?≥?3.25) on the initial images had more remarkable increased activity on the delayed images, while myocardium with lower FDG uptake (SUV_max?<?3.25) on the initial imaging had no increased uptake on delayed imaging. Increased FDG uptake was also observed in the bones on the delayed images. No significant changes of FDG uptake were noted in the parotid gland, thyroid gland, and prostate gland.

Conclusions

These findings may help nuclear medicine physicians when comparing images performed at different time points, when using FDG uptake in internal reference regions as a relative indicator of FDG uptake in a specific lesion, and when reading a delayed FDG PET imaging.     

Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction

Inflammatory-proteolytic processes in the vessel wall are essential in the pathophysiology of abdominal aortic aneurysm (AAA). It has been demonstrated that, ¹⁸F-FDG-PET/CT may be useful for detection of pathological wall metabolism and therefore risk stratification. Quantification of the FDG-uptake in AAA wall is hampered by partial-volume (PV)-effects. For correction and accurate quantitative ¹⁸F-FDG-uptake analysis we designed and validated a novel IDL-based software in correlation to phantom studies, histopathology and clinical presentation of AAA patients. For in vivo studies 23 patients with symptomatic and asymptomatic AAA underwent ¹⁸F-FDG-PET/CT before surgery. In areas with ¹⁸F-FDG-uptake the maximum and mean standardized uptake values in the vessel wall with (PVC-SUV_max, PVC-SUV_mean) and without (SUV_max, SUV_mean) PV-correction were determined. Results were correlated with clinical presentation, corresponding macrophage-infiltration and MMP-2- and -9-expression in surgical specimens. In patients, SUV_max, SUV_mean as well as PVC-SUV_max or PVC-SUV_mean enabled a highly significant (p < 0.005) discrimination of symptomatic and asymptomatic AAA. Uncorrected and corrected SUVs showed comparable correlations with macrophage-infiltration and MMP-9 expression. No correlation of ¹⁸F-FDG-uptake and MMP-2 was found. In vivo correlations of detected FDG-uptake with clinical and histological results showed comparable results for corrected and uncorrected SUVs. PV-correction is not mandatory for qualitative clinical assessment of glucose metabolism in the vessel wall of AAA-patients but may be necessary to establish quantitative cut off values to stratify patients for aneurysm repair.     

Single-Chain VEGF/Cy5.5 Targeting VEGF Receptors to Indicate Atherosclerotic Plaque Instability

Purpose

Unstable plaques may cause clinical events. Plaque destabilization results from the synergy between intraplaque angiogenesis and inflammation. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are considered to be involved in these processes. We investigated the efficacy of the anti-VEGFR mimic single-chain VEGF (scVEGF) to map intra-plaque VEGFR expression and atherosclerotic plaque instability using near-infrared fluorescence (NIRF).

Procedures

Human carotid plaques were retrieved from 15 symptomatic and five asymptomatic patients. NIRF plaque imaging was performed pre-/post-incubation with scVEGF/Cy5.5. Biopsies taken from regions with high (hot spot) and low (cold spot) NIRF signals were examined for VEGF-A, VEGFR-1 and VEGFR-2 mRNA expression levels using real-time RT-PCR analysis. Immunohistochemistry for CD31 (endothelium), CD68 (macrophages) and αSMA (smooth muscle cells) was performed to evaluate plaque composition.

Results

NIRF imaging of 20 plaques revealed a heterogeneous distribution of scVEGF/Cy5.5 binding. After incubation NIRF activity increased from 3.9×10^?5?±?5.2×10^?6 to 3.0×10^?4?±?2.2×10^?5 and 5.8×10^?5?±?1.9×10^?5 to 3.1×10^?4?±?1.9×10^?5 photons/s/cm²/sr/illumination intensity on the intraluminal and extraluminal side, respectively (both p?<?0.001). Real-time RT-PCR analysis showed a ~1.2- and ~16.4-fold increased mRNA expression of VEGFR-1 and VEGFR-2, respectively, in hot spots (vs. cold spots). Immunohistochemistry exhibited higher intraplaque capillary density in hot spots (vs. cold spots) (17.2?±?3.7 vs. 5.4?±?2.2 capillary/mm²; p?=?0.037). Hot spots contained significantly reduced numbers of α-SMA-positive cells (vs. cold spots) (2.2?±?0.7 % vs. 6.9?±?1.5 %; p?=?0.038). Finally, a ~2-fold increase of CD68⁺ infiltrating macrophages within hot spots (vs. cold spots) was observed (not significant, p?=?0.17). Significant higher capillary density in hot spots (vs. cold spots) was observed in plaques from symptomatic patients but not in plaques from asymptomatic patients.

Conclusion

Our data support that scVEGF/Cy5.5 is a suitable indicator for plaque instability and a promising diagnostic tool for risk assessment in cardiovascular diseases.     

The impact of radiotherapy on quality of life for cancer patients: a longitudinal study

Purpose

The aim of this study was to assess for changes in quality of life (QOL) among cancer patients who undergo radiotherapy (RT) and to identify factors that influence QOL in this group.

Materials and methods

Three hundred sixty-seven cancer patients who received curative RT were investigated using the EORTC QLQ-C30 questionnaire at the start of RT, end of RT, and 1 and 6 months post-RT.

Results

The patients were 49 % women, 51 % men, and median age at diagnosis was 57 years (range, 16–86 years). Compared to pre-RT, at the end of RT, the global health status score (p?<?0.001), nausea/vomiting (p?<?0.001), and apetite loss scores (p?<?0.001) were significantly poorer. Compared to the end of RT, at 1 and 6 months post-RT, global health status, all functional, and all symptom scores were significantly improved (p?<?0.001). Patient sex influenced scores for pain (p?=?0.036), appetite loss (p?=?0.027), and financial difficulty (p?=?0.003). Performance status influenced scores for global health status (p?=?0.006), physical functioning (p?<?0.001), cognitive functioning (p?=?0.001), and role functioning (p?=?0.021). Comorbidity influenced fatigue score (p?<?0.001). Cancer stage influenced scores for physical functioning (p?=?0.001), role functioning (p?=?0.010), and fatigue (p?<?0.001). Treatment modality (chemoRT vs. RT alone) influenced scores for physical functioning (p?=?0.016), fatigue (p?<?0.001), nausea/vomiting (p?=?0.009), and appetite loss (p?<?0.001); and RT field influenced scores for nausea/vomiting (p?=?0.001), appetite loss (p?=?0.003), and diarrhea (p?=?0.037). Radiotherapy dose functioning (p?<?0.001), cognitive functioning (p?<?0.001), social functioning (p?<?0.001), fatigue (p?<?0.001), and pain (<60 vs ≥60 Gy) had an effect on scores for physical functioning (p?<?0.001), role functioning (p?<?0.001), emotional (p?<?0.001), insomnia (p?<?0.001), constipation (p?<?0.001).

Conclusion

While RT negatively affects cancer patients’ QOL, restoration tends to be rapid and patients report significant improvement by 1 month post-RT. Various patient- and disease-specific factors and RT modality affect QOL in this patient group. We advocate measuring cancer patients’ QOL regularly as part of routine patient management.