Current Applications of PET/MR: Part II: Clinical Applications II.

Due to the major improvements in the hardware and image reconstruction algorithms, positron emission tomography/magnetic resonance imaging (PET/MR) is now a reliable state-of-the-art hybrid modality in medical practice. Currently, it can provide a broad range of advantages in preclinical and clinical imaging compared to single-modality imaging. In the second part of this review, we discussed the further clinical applications of PET/MR. In the chest, PET/MR has particular potential in the oncology setting, especially when utilizing ultrashort/zero echo time MR sequences. Furthermore, cardiac PET/MR can provide reliable information in evaluating myocardial inflammation, cardiac amyloidosis, myocardial perfusion, myocardial viability, atherosclerotic plaque, and cardiac masses. In gastrointestinal and hepato-pancreato-biliary malignancies, PET/MR is able to precisely detect metastases to the liver, being superior over the other imaging modalities. In genitourinary and gynaecology applications, PET/MR is a comprehensive diagnostic method, especially in prostate, endometrial, and cervical cancers. Its simultaneous acquisition has been shown to outperform other imaging techniques for the detection of pelvic nodal metastases and is also a reliable modality in radiation planning. Lastly, in haematologic malignancies, PET/MR can significantly enhance lymphoma diagnosis, particularly in detecting extra-nodal involvement. It can also comprehensively assess treatment-induced changes. Furthermore, PET/MR may soon become a routine in multiple myeloma management, being a one-stop shop for evaluating bone, bone marrow, and soft tissues.

68 Ga-PSMA-Avid Intranasal Solitary Fibrous Tumor.

ABSTRACT: The utility of molecular imaging in solitary fibrous tumors has not been fully established. We present a rare case of recurrent intranasal solitary fibrous tumor incidentally localized on 68 Ga-PSMA PET/CT scan, which turned out to be metabolically inactive on 18 F-FDG PET/CT.

The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer.

Radiolabelled prostate-specific membrane antigen (PSMA)-based PET-CT has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, and Lu-PSMA has been shown to be a potential new line of treatment for metastatic castration-resistant prostate cancer. Whole-body (WB) MRI has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multicentre studies comparing 68Ga-PSMA PET-CT and WB MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and also urinary excretion of tracers, which confounds image interpretation at the vesicoureteral junction. Additionally, studies have shown how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA+ lesions. Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes the accurate monitoring of treatment response to ADT with PSMA PET challenging. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB MRI. Emerging data support the wider adoption of PSMA PET and WB MRI for diagnosis, staging, disease burden evaluation and response monitoring, although their relative roles in the standard-of-care management of patients are yet to be fully defined.

Texture Analysis of Fractional Water Content Images Acquired during PET/MRI: Initial Evidence for an Association with Total Lesion Glycolysis, Survival and Gene Mutation Profile in Primary Colorectal Cancer.

To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42-83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: rs = -0.547, p = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowest: p = 0.017). For the most statistically significant prognostic marker, favorable prognosis was significantly associated with a higher number of GM per patient (medians: 7 vs. 1.5, p = 0.009). FWC-TA derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biological relevant information related to TLG, GM count, and provides prognostic information that can unlock new clinical applications for CRC patients.

Pitfalls on PET/MRI.

A decade of PET/MRI clinical imaging has passed and many of the pitfalls are similar to those on earlier studies. However, techniques to overcome them have emerged and continue to develop. Although clinically significant lung nodules are demonstrable, smaller nodules may be detected using ultrashort/zero echo-time (TE) lung MRI. Fast reconstruction ultrashort TE sequences have also been used to achieve high-resolution lung MRI even with free-breathing. The introduction and improvement of time-of-flight scanners and increasing the axial length of the PET detector arrays have more than doubled the sensitivity of the PET part of the system. MRI for attenuation correction has provided many potential pitfalls, including misclassification of tissue classes based on MRI information for attenuation correction. Although the use of short echo times have helped to address these pitfalls, one of the most exciting developments has been the use of deep learning algorithms and computational neural networks to rapidly provide soft tissue, fat, bone and air information for the attenuation correction as a supplement to the attenuation correction information from fat-water imaging. Challenges with motion correction, particularly respiratory and cardiac remain but are being addressed with respiratory monitors and using PET data. In order to address truncation artefacts, the system manufacturers have developed methods to extend the MR field-of-view for the purpose of the attenuation and scatter corrections. General pitfalls like stitching of body sections for individual studies, optimum delivery of images for viewing and reporting, and resource implications for the sheer volume of data generated remain Methods to overcome these pitfalls serve as a strong foundation for the future of PET/MRI. Advances in the underlying technology with significant evolution in hard-ware and software and the exiting developments in use of deep learning algorithms and computational neural networks will drive the next decade of PET/MRI imaging.

FDG-PET/CT in colorectal cancer: potential for vascular-metabolic imaging to provide markers of prognosis.

PURPOSE: This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. METHODS: This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. RESULTS: A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon - high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441-8.333), p = 0.006; M0rectum - high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901-10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162-5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. CONCLUSION: Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study.

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.

Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial.

PURPOSE: Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer. METHODS AND MATERIALS: Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety. RESULTS: 18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]). CONCLUSIONS: 18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy.

Imaging of Prostate Cancer Recurrence in the Vas Deferens With 68Ga-PSMA PET/CT.

Two cases with Ga-PSMA-avid prostate cancer recurrence in the vas deferens are presented. These cases highlight the clinical importance of imaging the pattern of local prostate cancer recurrence and the potential difficulties that arise due to the altered anatomy in the prostate bed after prostatectomy or radiotherapy.

Challenges in glucoCEST MR body imaging at 3 Tesla.

BACKGROUND: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. METHODS: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. RESULTS: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T2, B1 saturation power and integration range. Our results show that motion correction and B0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. CONCLUSIONS: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B1 + and B0 render the originally small glucoCEST signal difficult to detect.

Correction to: The clinical utility of prostate cancer heterogeneity using texture analysis of multiparametric MRI.

Unfortunately, in the original article one co-author's name is missing. The co-author name and affiliation is given as follows.

UK guidelines on 18F-fluciclovine PET/CT in prostate cancer imaging.

The purpose of these guidelines is to assist specialists in Nuclear Medicine and Radionuclide Radiology in recommending, performing, interpreting and reporting F-fluciclovine PET/computed tomography. It should be recognised that adherence to the guidance in this document will not assure an accurate diagnosis or a successful outcome. These guidelines will assist individual departments in the formulation of their own local protocols. The guidelines apply to studies on adults. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient in order to deliver effective and safe medical care.

The clinical utility of prostate cancer heterogeneity using texture analysis of multiparametric MRI.

PURPOSE: To determine if multiparametric MRI (mpMRI) derived filtration-histogram based texture analysis (TA) can differentiate between different Gleason scores (GS) and the D'Amico risk in prostate cancer. METHODS: We retrospectively studied patients whose pre-operative 1.5T mpMRI had shown a visible tumour and who subsequently underwent radical prostatectomy (RP). Guided by tumour location from the histopathology report, we drew a region of interest around the dominant visible lesion on a single axial slice on the T2, Apparent Diffusion Coefficient (ADC) map and early arterial phase post-contrast T1 image. We then performed TA with a filtration-histogram software (TexRAD -Feedback Medical Ltd, Cambridge, UK). We correlated GS and D'Amico risk with texture using the Spearman's rank correlation test. RESULTS: We had 26 RP patients with an MR-visible tumour. Mean of positive pixels (MPP) on ADC showed a significant negative correlation with GS at coarse texture scales. MPP showed a significant negative correlation with GS without filtration and with medium filtration. MRI contrast texture without filtration showed a significant, negative correlation with D'Amico score. MR T2 texture showed a significant, negative correlation with the D'Amico risk, particularly at textures without filtration, medium texture scales and coarse texture scales. CONCLUSION: ADC map mpMRI TA correlated negatively with GS, and T2 and post-contrast images with the D'Amico risk score. These associations may allow for better assessment of disease prognosis and a non-invasive method of follow-up for patients on surveillance. Further, identifying clinically significant prostate cancer is essential to reduce harm from over-diagnosis and over-treatment.

68Ga-Prostate-Specific Membrane Antigen PET/CT: Incidental Finding of a Liposarcoma.

This case highlights that liposarcoma shows Ga-prostate-specific membrane antigen avidity and should be included in the differential diagnosis of patients with avid muscle lesions to avoid an incorrect diagnosis of metastasis.

Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

BACKGROUND: A certain proportion of patients with locally advanced rectal cancer experience complete response after undergoing neoadjuvant chemoradiotherapy. These patients might be suitable for a conservative "watch and wait" approach, avoiding high-morbidity surgery. Texture analysis is a new modality that can assess heterogeneity in medical images by statistically analyzing gray-level intensities on a pixel-by-pixel basis. This study hypothesizes that texture analysis of magnetic resonance images can identify patients with a complete response. OBJECTIVE: This study aims to determine whether texture analysis of magnetic resonance images as a quantitative imaging biomarker can accurately identify patients with complete response. DESIGN: This is a retrospective diagnostic accuracy study. SETTINGS: This study was conducted at Colchester General Hospital, January 2003 to 2014. PATIENTS: All patients diagnosed with locally advanced rectal cancer who underwent long-course chemoradiotherapy had a posttreatment magnetic resonance scan and underwent surgery are included. INTERVENTION: Texture analysis was extracted from T2-weighted magnetic resonance images of the rectal cancer. MAIN OUTCOME MEASURES: Textural features that are able to identify complete responders were identified by a Mann-Whitney U test. Their diagnostic accuracy in identifying complete responders was determined by the area under the receiver operator characteristics curve. Cutoff values were determined by the Youden index. Pathology was the standard of reference. RESULTS: One hundred fourteen patients with first posttreatment MRI scans (6.2 weeks after completion of neoadjuvant treatment) were included. Sixty-eight patients had a second posttreatment scan (10.4 weeks). With no filtration, mean (p = 0.033), SD (p = 0.048), entropy (p = 0.007), and skewness (p = 0.000) from first posttreatment scans, and SD (p = 0.042), entropy (p = 0.014), mean of positive pixels (p = 0.032), and skewness (p = 0.000) from second posttreatment scans were all able to identify complete response. Area under the curve ranged from 0.750 to 0.88. LIMITATIONS: Texture analysis of MRI is a new modality; therefore, further studies are necessary to standardize the methodology of extraction of texture features, timing of scans, and acquisition parameters. CONCLUSIONS: Texture analysis of MRI is a potentially significant imaging biomarker that can accurately identify patients who have experienced complete response and might be suitable for a nonsurgical approach. (Cinicaltrials.gov:NCT02439086). See Video Abstract at http://links.lww.com/DCR/A760.

Prostate-specific membrane antigen positron emission tomography in the management of recurrent prostate cancer.

Introduction: There is an unmet clinical need for early, accurate imaging of recurrent prostate cancer to improve patient outcomes. Staging, by conventional bone scintigraphy and CT have become outdated. 68Ga-PSMA PET/CT imaging in this setting has developed rapidly, with widespread International adoption in line with evidence-based guidelines in this group of patients. Sources of data: A PubMed search of English language articles was performed using following keywords: PSMA, PET/CT, biochemical recurrence, prostate cancer. The search revealed 85 articles, of which 75 were original; 70 of these involved use of the most widely available type of PSMA tracer (HBED). The review also relied on the clinical experience of reporting over 1000 PSMA PET/CT studies at a major tertiary referral centre for uro-oncology, with the majority of cases having been performed in the biochemical recurrence setting from 2015 to 2018. Areas of agreement: 68Ga-PSMA PET is a game changer and superior to choline PET and other established tracers which have been used in prostate cancer evaluation. Detection of recurrence at the prostate bed remains challenging due to bladder and urethral tracer accumulation. The main strength of PSMA PET/CT is its ability to identify small (<8 mm) pathological lymph nodes, upstaging nodal status in up to two-thirds of cases. Additionally, PSMA PET/CT, detects bone and bone marrow metastases missed by conventional bone and CT imaging. Thus, PSMA PET/CT has major impact on patient management, with studies reporting overall changes in 39-76% of cases. Areas of controversy: Controversy exists regarding patient access and NHS affordability of PSMA PET/CT imaging. Currently, no reimbursement is available under the NHS tariff system. The cost outlay for tertiary hospital linked PET centres ranges from £150-170 K. Large referral volumes, and technical advances in manufacturing process will make this tracer cost neutral and similar to the current funded, but less sensitive, choline PET. Current NICE guidelines for prostate cancer management do not include a recommendation on when PSMA PET/CT should be used and this is likely to remain the case in the next revision, due in 2019. Growing points: Although PSMA PET/CT imaging results in significant management change, there is a need for high quality economic evaluation and cost analysis for this modality. Lack of this data will result in poor adoption of this technique and thus limit patient access. Furthermore, it is hoped that future tracers will become even more sensitive and identify disease at earlier thresholds. Areas timely for developing research: Well-designed clinical trials with consideration of the health economic benefit of using PSMA PET/CT will be essential to provide a basis for entry into guidelines such as NICE and to provide a rationale for reimbursement.

Phenotypic appearances of prostate utilizing PET-MRI and PET-CT with 68Ga-PSMA, radiolabelled choline and 68Ga-DOTATATE.

The objective of this study was to highlight the role of multimodality imaging and present the differential diagnosis of abnormal tracer accumulation in the prostate and periprostatic tissue. Our departments have performed molecular imaging of the prostate utilizing PET-CT and PET-MRI with a range of biomarkers including F-FDG, radiolabelled choline, Ga-DOTATATE PET-CT and Ga-PSMA images. We retrospectively reviewed the varying appearances of the prostate gland in different diseases and incidental findings in periprostatic region. The differential diagnosis of pathologies related to prostate and periprostatic tissue on multimodality imaging includes malakoplakia, rhabdomyosarcoma, lymphoma, prostate cancer, neuroendocrine tumours, uchida changes, rectoprostatic fistula, synchronous malignancies, lymphocoele and schwanoma. There exists a wide differential for abnormal tracer accumulation in the prostate gland. As a radiologist and nuclear medicine physician, it is important to be aware of range of prostatic and periprostatic pathologies.

Impact of 68Ga-Prostate-Specific Membrane Antigen PET/CT on Prostate Cancer Management.

The objective of this study was to assess the impact of 68Ga-prostate-specific membrane antigen (68Ga-PSMA) PET/CT on the management of prostate cancer in patients with biochemical recurrence (BCR). Methods: Documented management plans before and after 68Ga-PSMA PET/CT in 100 patients with BCR were retrospectively reviewed, and changes in plans were recorded. Results: Management changed after 68Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23 (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients previously treated with radical radiotherapy. Positive scan results (P < 0.001) and higher prostate-specific antigen (PSA) levels (P = 0.024) were associated with management changes. No significant association with management change was found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or PSA doubling time. Conclusion:68Ga-PSMA PET/CT altered management in 39% of patients with BCR, and changes occurred more often in patients with radical radiotherapy treatment, positive 68Ga-PSMA scan results, and higher PSA levels.