Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

Potential Added Value of 18F-FDG PET Metabolic Parameters in Predicting Disease Relapse in Type 1 Autoimmune Pancreatitis.

BACKGROUND: The predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters for predicting AIP relapse is currently unknown. This study firstly explored the value of 18F-FDG PET/CT parameters as predictors of type 1 AIP relapse. METHODS: This multicenter retrospective cohort study analyzed 51 patients who received 18F-FDG PET/CT prior to treatment and did not receive maintenance therapy after remission. The study collected baseline characteristics and clinical data and conducted qualitative and semi-quantitative analysis of pancreatic lesions and extrapancreatic organs. The study used three thresholds to select the boundaries of pancreatic lesions to evaluate metabolic parameters, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal liver standard uptake value ratio (SUVR). Univariate and multivariate analyses were performed to identify independent predictors and build a recurrence prediction model. The model was internally validated using the bootstrap method and a nomogram was created for clinical application. RESULTS: In the univariable analysis, the relapsed group showed higher levels of SUVmax (6.0 ± 1.6 vs. 5.2 ± 1.1; P = 0.047), SUVR (2.3 [2.0-3.0] vs. 2.0 [1.6-2.4]; P = 0.026), and TLG2.5 (234.5 ± 149.1 vs. 139.6 ± 102.5; P = 0.020) among the 18F-FDG PET metabolic parameters compared to the non-relapsed group. In the multivariable analysis, serum IgG4 (OR, 1.001; 95% CI, 1.000-1.002; P = 0.014) and TLG2.5 (OR, 1.007; 95% CI, 1.002-1.013; P = 0.012) were independent predictors associated with relapse of type 1 AIP. A receiver-operating characteristic curve of the predictive model with these two predictors demonstrated an area under the curve of 0.806. CONCLUSION: 18F-FDG PET/CT metabolic parameters, particularly TLG2.5, are potential predictors for relapse in patients with type 1 AIP. A multiparameter model that includes IgG4 and TLG2.5 can enhance the ability to predict AIP relapse.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis.

OBJECTIVE: To evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis. PATIENTS AND METHODS: In total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy. RESULTS: The ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA. CONCLUSIONS: The multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging.

PURPOSE: To investigate the potential of a novel Al18F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies. METHODS: Al18F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (PSMA -) cell lines. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of Al18F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with 18F-DCFPyL were performed. PET/CT imaging was performed on 8 healthy volunteers and 20 newly diagnosed PCa patients at 1 h post-injection (p.i.). The biodistribution in human and preliminary diagnostic efficacy of Al18F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software. RESULT: Qualified Al18F-PSMA-Q was efficiently prepared with a non-decay-corrected radiochemical yield (RCY) of 22.0-28.3%, a specific activity (SA) of > 50 GBq/µmol. The hydrophilicity was comparably high with a log P value of - 3.69 ± 0.39. Al18F-PSMA-Q was found to bind to PSMA specifically with a Ki value of 17.05 ± 1.14 nM. The distribution and elimination half-lives of Al18F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of 18F-DCFPyL. Micro-PET imaging of Al18F-PSMA-Q can clearly differentiate 22Rv1 tumors from PC-3 tumors and background with a high SUVmax of 2.17 ± 0.42 and a tumor-to-muscle ratio of 84.37 ± 31.62, which were higher than those of 18F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al18F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al18F-PSMA-Q was observed in organs physiologically expressing PSMA. Twenty-six tumor lesions were detected in 20 PCa patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 19.71 ± 16.52, 5.11, 31.30 ± 29.85, and 44.77 ± 22.29, respectively. The mean SUVmax of tumors in patients with PSA > 10 ng/mL was significantly higher than that in patients with PSA ≤ 10 ng/mL (25.97 ± 18.64 vs. 10.33 ± 3.74). Meanwhile, the mean SUVmax of tumors in patients with a Gleason score ≥ 8 was significantly higher than that in patients with a Gleason score < 8 (31.85 ± 22.09 vs. 13.18 ± 11.58). The kidneys received the highest estimated dose of 0.098 ± 0.006 mGy/MBq, and the effective dose was calculated as 0.0128 ± 0.007 mGy/MBq. CONCLUSION: The novel qualified PSMA-targeted radiotracer Al18F-PSMA-Q was conveniently prepared with favorable yield and SA. The results of preclinical and pilot clinical studies exhibited a high specific uptake in PCa lesions and an excellent tumor-to-background ratio with a reasonable radiation exposure, which indicated the great potential of Al18F-PSMA-Q for PCa imaging. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.

Targeted fluorescent imaging of a novel FITC-labeled PSMA ligand in prostate cancer.

In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(-) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.

Sporadic adult-onset neuronal intranuclear inclusion disease without high-intensity signal on DWI and T2WI: a case report.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in cells in the central and peripheral nervous system. High-intensity signal in the corticomedullary junction on diffusion-weighted imaging (DWI) is supportive to the diagnosis of NIID. We describe a patient with sporadic adult-onset NIID but without any high-intensity signal on DWI and T2-weighted imaging (T2WI). CASE PRESENTATION: A 58-year-old woman without special family history developed mild persistent tremor in the right hand and deteriorated 2 years later. At 60 years of age, the patient began to conceive the bank, police and internet being deceptive, further presented apathy and confusion after two and a half years, as well as fabrication of non-existent things. Despite the treatment of antipsychotic drugs due to a diagnosis of mental disorder, the patient appeared weakness in the right limbs. Neurological examination revealed mutism, resting tremor, cogwheel-like rigidity in upper limbs, and weakness in all limbs. Brain magnetic resonance imaging displayed no cerebral atrophy initially but atrophy of frontal, temporal and parietal lobes 5 years later. No any high-intensity signal on DWI and T2WI was revealed. However, hypometabolism in the cortexes with atrophy and the right putamen nucleus were showed on 18F-fluoro-deoxy-glucose positron emission tomography/magnetic resonance. On the basis of 107 GGC repeats (normal number <40) in NOTCH2NLC gene and intranuclear inclusions with p62 immunoreactivity in the adipocyte of cutaneous sweat duct by skin biopsy, NIID was finally diagnosed. The symptomatic treatment was given but the patient had no evident improvement. CONCLUSIONS: Our case highlights that despite the lack of high-intensity signal on DWI and T2WI, NIID is still considered for patients with parkinsonism and mental impairment.

Medication overuse headache associated with decreased dopamine transporter availability in the medial but not in the lateral orbitofrontal cortex: a 11CFT PET/MR study.

BACKGROUNDS: Dysfunction of the mesocorticolimbic dopamine system in medication overuse headache (MOH) is unknown. This study aimed to determine dopamine transporter (DAT) availability, which is sensitive to dopamine levels, in the mesocorticolimbic dopamine system in MOH patients. METHODS: This case-control study investigated eligible MOH patients admitted to the International Headache Centre in the neurological department of Chinese PLA General Hospital between July 2018 and August 2019. All subjects underwent an integrated positron emission tomography (PET)/magnetic resonance (MR) brain scans with 11CFT, a radioligand that binds to DAT. Standardised uptake value ratio (SUVr) images were compared voxelwise between MOH patients and healthy controls (HCs). SUVr values from significantly changed regions were extracted, and partial correlation analyses with clinical measures were conducted. RESULTS: We examined 17 MOH patients and 16 HCs. MOH patients had lower SUVr levels in the medial rather than lateral orbitofrontal cortex (OFC) than HCs (T = -5.0317, PGRF < 0.01), which showed no correlation with clinical features. CONCLUSIONS: MOH is characterised by decreased DAT availability in the medial OFC, which might reflect compensatory downregulation due to low dopamine signalling within the mesocorticolimbic dopamine system and provide a new perspective to understand the pathogenesis of MOH.

A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer.

Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the neurovascular bundles (NVBs) as much as possible. The objective of this study was to synthesize a PSMA fluorescent probe (PSMA-Cy5) and verify the targeting specificity of the probe for prostate cancer, thereby providing a theoretical basis for the development of PSMA fluorescent probes for clinical application in the future. Methods: In this study, a novel water-soluble 3H-indocyanine-type bioluminescent dye-Cy5-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-Cy5) was synthesized by liquid phase synthesis. The PSMA ligand was developed based on the glutamine-urea-lysine (Glu-urea-Lys) structure. The new fluorescent probe was evaluated in vitro and in vivo, and its safety was evaluated. Confocal microscopy was used to observe the binding uptake of PSMA-Cy5 with PSMA (+) LNCaP cells, PSMA (-) PC3 cells and blocked LNCaP cells. In in vivo optical imaging studies, the targeting specificity of PSMA (+) 22Rv1 tumors to probe binding was validated by tail vein injection of PSMA-Cy5. The safety of the PSMA-Cy5 probe was evaluated by histopathological analysis of mouse organs by a single high-dose tail vein injection of PSMA-Cy5. Results: In vitro fluorescence cell uptake experiments showed that the binding of PSMA-Cy5 to LNCaP cells has targeting specificity. PC3 cells and blocked LNCaP cells showed almost no uptake. The results of in vivo optical imaging studies showed that the tumor-to-background ratio in the 22Rv1 group was 3.39 ± 0.47; in the 22Rv1 blocking group it was 0.78 ± 0.15, and in the PC3 group it was 0.94 ± 0.09, consistent with the in vitro results. After a high-dose injection of PSMA-Cy5, there were no abnormalities in the tissues or organs of the mice. The probe showed good safety. Conclusions: PSMA-Cy5 is a probe with good targeting specificity and low toxicity that can accurately visualize tumors in vivo. This study has an important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to precise tumor imaging during radical prostatectomy to reduce the incidence of postoperative PSM.

Comparison between 18 F-DCFPyL PET and MRI for the detection of transition zone prostate cancer.

BACKGROUND: We aimed to compare the diagnostic performance of 18 F-DCFPyL positron emission tomography (PET) and multiparameter magnetic resonance imaging (mp-MRI) in detecting transition zone (TZ) prostate cancer (PCa). METHODS: This retrospective study included 20 patients who underwent 18 F-DCFPyL PET/MRI and 32 patients who underwent 18 F-DCFPyL PET/CT and MRI from January 2019 to June 2020. All patients had TZ lesions and underwent prostate biopsies. One senior (reader 1) and one junior (reader 2) nuclear medicine physician evaluated each TZ lesion independently, according to the molecular imaging prostate-specific membrane antigen scoring system and the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). The histologic diagnosis of prostate biopsy was used as the reference standard. The diagnostic performance of the two methods was compared in terms of inter-reader agreement and area under the receiver operating characteristic (AUC-ROC) curve. RESULTS: Of the 52 patients, 43 had TZ PCa. For inter-reader agreement, the kappa value was 0.883 for 18 F-DCFPyL PET and 0.393 for mp-MRI. For PET, both readers had the same diagnostic sensitivity, specificity, and accuracy of 93.0%, 77.8%, and 90.4%, respectively. For mp-MRI, the diagnostic sensitivity, specificity, and accuracy was 67.4%, 33.3%, and 61.5% for reader 1, and 51.2%, 44.4%, and 51.9% for reader 2, respectively. PET outperformed mp-MRI for both readers with an AUC of 0.872 for PET versus 0.584 for mp-MRI, p = .0209 for reader 1, and an AUC of 0.860 for PET versus 0.505 for mp-MRI, p = .0213 for reader 2. Among the 43 patients with TZ PCa, 18 F-DCFPyL PET detected a distant bone metastasis missed by the CT in one case and two small lymph node metastases missed by the CT and MRI in another case. CONCLUSIONS: These results suggest that 18 F-DCFPyL PET, which was almost independent of the experience of the readers, was more objective in the evaluation of TZ lesions, and had higher diagnostic value than mp-MRI.

Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging?

PURPOSE: PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose an optimized dose regimen to yield a constant image quality independent of patient habitus to meet the clinical needs. METHODS: A first patient cohort of 78 consecutive oncological patients (59.7 ± 13.7 years) who underwent a total-body PET/CT scan were retrospectively enrolled to develop the regimen. The patients were randomly distributed in four body mass index (BMI) groups according to the World Health Organization (WHO) criteria. The liver SNR (signal-to-noise ratio, SNRL) was obtained by manually drawing regions of interest (ROIs) and normalized (SNRnorm) by the product of injected activity and acquisition time. Fits of SNRnorm against different patient-dependent parameters were performed to determine the best correlating parameter and fit method. A qualitative assessment on image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL. Thus, an optimized regimen was proposed and validated by a second patient cohort consisted of prospectively enrolled 38 oncological patients. RESULTS: The linear fit showed SNRnorm had the strongest correlation (R2 = 0.69) with the BMI than other patient-dependent parameters and fit method. The qualitative assessment indicated a SNRL value of 14.0 as an acceptable threshold to achieve sufficient image quality. The optimized dose regimen was determined as a quadratic relation with BMI: injected activity (MBq) = 39.2 (MBq)/(- 0.03*BMI + 1.49)2. In the validation study, the SNRL no longer decreased with the increase of BMI. There was no significant difference of the image quality regarding the value of SNRL between different BMI groups (p > 0.05). In addition, the injected activity was reduced by 75.6 ± 2.9%, 72.1 ± 4.0%, 67.1 ± 4.4%, and 64.8 ± 3.5% compared with the first cohort for the four BMI groups, respectively. CONCLUSION: The study proposed a quadratic relation between the 18F-FDG injected activity and the patient's BMI for total-body 18F-FDG PET imaging. In this regimen, the image quality can maintain in a constant level independent of patient habitus and meet the clinical requirement with a reduced injected activity.

Etiologic classification of infantile spasms using positron emission/magnetic resonance imaging and the efficacy of adrenocorticotropic hormone therapy.

PURPOSE: The aim of this study was to investigate if the etiologic classification of infantile spasm (IS) using positron emission tomography/magnetic resonance imaging (PET/MR) is feasible. Based on the classified etiologic groups, we further evaluated the efficacy of adrenocorticotropic hormone (ACTH) therapy in different IS groups. MATERIALS AND METHODS: One hundred fifty-five children diagnosed with IS were included in this study. A qualitative assessment of the PET/MR images was performed. The abnormal lesions localized with both MR and PET images were considered to be epileptic foci, and the patients with these lesions were classified into the structural-metabolic group. For the remaining patients, quantitative analyses were further performed on whole-brain T1-weighted (T1WI) and PET images, based on the asymmetry index of bilateral volumes and metabolic quantifications. Patients with asymmetry indices above a certain threshold (15%) were classified into the structural-metabolic group. The patients without positive finding from either qualitative or quantitative analyses were assigned to the unknown etiology group. The efficacy of ACTH therapy was evaluated in the different IS groups. RESULTS: Among the 155 children with IS, 18 genetic cases were first diagnosed by the genetic testing. In the remaining 137 cases, 49 cases were identified with structural-metabolic etiology using qualitative PET/MR assessments. Fifty-two cases were newly diagnosed with quantitative analysis. The remaining 36 cases were classified into the unknown etiology group. The efficacy of ACTH therapy was statistically different for the different etiology groups (p < 0.001). The respective efficacy rates for the genetic, qualitative structural-metabolic, quantitative structural-metabolic, and unknown etiology groups were 27.8% (5/18), 30.61% (15/49), 34.62% (18/52), and 72.22% (26/36), respectively. CONCLUSIONS: The combination of PET and MR provides additional diagnostic information for IS. Quantitative analysis can further improve patient etiologic classifications and the predication of therapy efficacies.

PET image denoising using unsupervised deep learning.

PURPOSE: Image quality of positron emission tomography (PET) is limited by various physical degradation factors. Our study aims to perform PET image denoising by utilizing prior information from the same patient. The proposed method is based on unsupervised deep learning, where no training pairs are needed. METHODS: In this method, the prior high-quality image from the patient was employed as the network input and the noisy PET image itself was treated as the training label. Constrained by the network structure and the prior image input, the network was trained to learn the intrinsic structure information from the noisy image and output a restored PET image. To validate the performance of the proposed method, a computer simulation study based on the BrainWeb phantom was first performed. A 68Ga-PRGD2 PET/CT dataset containing 10 patients and a 18F-FDG PET/MR dataset containing 30 patients were later on used for clinical data evaluation. The Gaussian, non-local mean (NLM) using CT/MR image as priors, BM4D, and Deep Decoder methods were included as reference methods. The contrast-to-noise ratio (CNR) improvements were used to rank different methods based on Wilcoxon signed-rank test. RESULTS: For the simulation study, contrast recovery coefficient (CRC) vs. standard deviation (STD) curves showed that the proposed method achieved the best performance regarding the bias-variance tradeoff. For the clinical PET/CT dataset, the proposed method achieved the highest CNR improvement ratio (53.35% ± 21.78%), compared with the Gaussian (12.64% ± 6.15%, P = 0.002), NLM guided by CT (24.35% ± 16.30%, P = 0.002), BM4D (38.31% ± 20.26%, P = 0.002), and Deep Decoder (41.67% ± 22.28%, P = 0.002) methods. For the clinical PET/MR dataset, the CNR improvement ratio of the proposed method achieved 46.80% ± 25.23%, higher than the Gaussian (18.16% ± 10.02%, P < 0.0001), NLM guided by MR (25.36% ± 19.48%, P < 0.0001), BM4D (37.02% ± 21.38%, P < 0.0001), and Deep Decoder (30.03% ± 20.64%, P < 0.0001) methods. Restored images for all the datasets demonstrate that the proposed method can effectively smooth out the noise while recovering image details. CONCLUSION: The proposed unsupervised deep learning framework provides excellent image restoration effects, outperforming the Gaussian, NLM methods, BM4D, and Deep Decoder methods.

A Novel Scatter Correction Method for Cone-Beam Computed Tomography.

In this article, a novel scatter correction approach was proposed based on the Klein-Nishina formulation. Through a series of deductions from this formulation, a principle was proposed that the photon intensity distribution was determined by the attenuation coefficient µ and the path length l. This means if 2 pencil beams pass through 2 objects with the same µl, even if the attenuation coefficient µ and the path length l of the objects are different, they will still achieve the same photon intensity distribution, that is, the same point spread function. Subsequently, a novel scatter correction approach was established after a series of deductions based on this principle. The simulations and experiments demonstrated the correctness of our principle and the comparable correction effect of our scatter correction approach compared with the beam stop array method. Furthermore, because of the character of our method, the program has very high parallel computing features, which can dramatically increase the computation speed.

Glomerular filtration rate measured by (99m) Tc-DTPA renal dynamic imaging is significantly lower than that estimated by the CKD-EPI equation in horseshoe kidney patients.

AIM: Gate's glomerular filtration rate (gGFR) measured by (99m) Tc-DTPA renal dynamic imaging and estimated GFR (eGFR) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation are two indexes used to evaluate renal function. However, little is known about whether gGFR can be used to accurately assess renal function in horseshoe kidney (HSK) patients with renal fusion anomalies. METHODS: Nineteen HSK patients (HSK group) diagnosed by renal imaging and 38 CKD patients with "normal kidney shape" (non-HSK group) matched to the HSK patients in terms of gender, age and biochemical indicators at Chinese PLA General Hospital were enrolled in this study. Gender, age, serum total protein (TP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), gGFR and eGFR were recorded and analyzed using χ(2) test, t-test, and Wilcoxon test which was presented as median(IQR). RESULTS: (1) There were no significant differences in gender, age, TP, ALB, BUN, Scr, or eGFR between these two groups. (2) In HSK patients, the renogram showed abnormal renal axis with the lower poles orientated medially. The timed uptake curve showed that the isotope excretion in the HSK group was slower than that in the non-HSK group. (3) For all HSK patients, gGFR was significantly lower than eGFR (range -12.52 mL/min per 1.73m(2) to -93.18 mL/min per 1.73m(2) ). There was no significant difference in eGFR between the HSK [96.42 (36.02) mL/min per 1.73 m(2) ] and non-HSK groups [94.46 (33.00) mL/min per 1.73 m(2) ]. The gGFR of the HSK group [41.18 (16.60) mL/min per 1.73m(2) ] was much lower than that of the non-HSK group [86.42(26.40) mL/min per 1.73m(2) , P < 0.001] and the eGFR of the HSK group (P < 0.001). The gGFR and eGFR of the non-HSK group were not significantly different. CONCLUSION: gGFR measured by (99m) Tc-DTPA renal dynamic imaging is significantly lower than eGFR estimated by the CKD-EPI equation, which indicates that isotope renogram cannot accurately evaluate the GFR of HSK patients.

Evaluation of a Wobbling Method Applied to Correcting Defective Pixels of CZT Detectors in SPECT Imaging.

In this paper, we propose a wobbling method to correct bad pixels in cadmium zinc telluride (CZT) detectors, using information of related images. We build up an automated device that realizes the wobbling correction for small animal Single Photon Emission Computed Tomography (SPECT) imaging. The wobbling correction method is applied to various constellations of defective pixels. The corrected images are compared with the results of conventional interpolation method, and the correction effectiveness is evaluated quantitatively using the factor of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). In summary, the proposed wobbling method, equipped with the automatic mechanical system, provides a better image quality for correcting defective pixels, which could be used for all pixelated detectors for molecular imaging.

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

Although (18) F-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 (18) F-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 (SUV(max)) and (SUV(mean)) 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 SUV(max) measurements of FDG were significantly different between aggressive and indolent B-cell non-Hodgkin lymphoma. The receiver operating characteristic curve of SUV(max) of tumour/liver for FDG studies resulted in the most area under the curve. The SUV(max) 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 (18) F-FLT should employ the tumour/mediastinum SUV(max) ratio for accurate uptake measurement.

Comparison of dual-biomarker PIB-PET and dual-tracer PET in AD diagnosis.

OBJECTIVES: To identify the optimal time window for capturing perfusion information from early (11)C-PIB imaging frames (perfusion PIB, (11)C-pPIB) and to compare the performance of (18)F-FDG PET and "dual biomarker" (11)C-PIB PET [(11)C-pPIB and amyloid PIB ((11)C-aPIB)] for classification of AD, MCI and CN subjects. METHODS: Forty subjects (14 CN, 12 MCI and 14 AD patients) underwent (18)F-FDG and (11)C-PIB PET studies. Pearson correlation between the (18)F-FDG image and sum of early (11)C-PIB frames was maximised to identify the optimal time window for (11)C-pPIB. The classification power of imaging parameters was evaluated with a leave-one-out validation. RESULTS: A 7-min time window yielded the highest correlation between (18)F-FDG and (11)C-pPIB. (11)C-pPIB and (18)F-FDG images shared a similar radioactive distribution pattern. (18)F-FDG performed better than (11)C-pPIB for the classification of both AD vs. CN and MCI vs. CN. (11)C-pPIB + (11)C-aPIB and (18)F-FDG + (11)C-aPIB yielded the highest classification accuracy for the classification of AD vs. CN, and (18)F-FDG + (11)C-aPIB had the best classification performance for the classification of MCI vs. CN CONCLUSION: C-pPIB could serve as a useful biomarker of rCBF for measuring neural activity and improve the diagnostic power of PET for AD in conjunction with (11)C-aPIB. (18)F-FDG and (11)C-PIB dual-tracer PET examination could better detect MCI. KEY POINTS: • Dual-tracer PET examination provides neurofunctional and neuropathological information for AD diagnosis. • The identified optimal 11C-pPIB time frames had highest correlation with 18F-FDG. • 11C-pPIB images shared a similar radioactive distribution pattern with 18F-FDG images. • 11C-pPIB can provide neurofunctional information. • Dual-tracer PET examination could better detect MCI.