Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

PURPOSE To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings

Hematopoietic islands mimicking osteoblastic metastases within the axial skeleton

Background Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity and can confuse with osteoblastic metastases. This study aimed to characterize typical MRI and CT findings of hematopoietic islands in distinction from osteoblastic metastases to help both radiologists and clinicians, on the one hand, not to overdiagnose this entity and, on the other hand, to decide on a reasonable work-up. Methods We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age = 65.5 years [range, 49–74]) who received both MRI and CT at initial diagnosis between 2006 and 2020. CT-guided biopsy was performed in five cases to confirm the diagnosis, while the other five patients received long-term MRI follow-up (median follow-up = 28 months [range, 6–96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging respectively 18 F- fluorodeoxyglucose PET/CT in two, and Technetium 99 m skeletal scintigraphy in one of the patients. Results All lesions were small (mean size = 1.72 cm 2 ) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared isointense to slightly hyperintense on STIR images and slightly enhanced after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis. Conclusions Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis in most cases

Molecular Imaging of Prostate Cancer

Chapter 1 addresses the introduction to the thesis and provides epidemiology, etiology, metastatic spread, current diagnostics and clinical need of new biomarker for risk stratification of prostate cancer. Chapter 2 provides a detailed analysis of the distribution pattern of the three most used choline tracers: 18F-methylcholine, 11C-choline, and 18F-ethylcholine in metabolically and anatomically disease-free patients. The ranges of SUVmax, SUVmean and standard deviations have been presented. Potential pitfalls in evaluation of “non-avid” but clinically significant presentation of different disease entities are also addressed. The chapter provides overview of the variations in choline uptake pattern which is vital for assessment of various organs when imaging is performed for evaluation of metastatic disease. Chapter 3 presents the feasibility of assessing dynamic 18F Ethyl Choline PET with a view to do kinetic modelling in clinical setting of biochemical relapse of Prostate Cancer. This critical piece of work underpins the quantification, tracer kinetics and demonstrates that cancerous tissue shows abnormal perfusion. From these observations I was able to conclude that 18F Choline can act as a biomarker to assess angiogenesis in prostate cancer and introduces 18F Choline as a biomarker for further work presented in chapter 4-8. Chapter 4 addresses the detection of clinically significant and insignificant prostate cancer on 18F-FECH PET/CT and I correlated findings with template guided prostate mapping biopsy (TPM). Sensitivity and Specificity data of 8F-FECH PET/CT has been provided. Chapter 5 addresses the accuracy of 18F Choline PET/MR which is compared to reference standard (template guided prostate mapping biopsy). This work suggests that data obtained from 18F Choline PET/MR can allow detection of clinically significant and insignificant prostate cancer. I noted that multiple previous treatments can give false positive results and 18F Choline PET/MR is the imaging investigation of choice post HIFU. Moreover, false negative results with 18F Choline PET/MR can be due to very small volume (=/<2 mm) disease. Chapter 6 presents the differential diagnosis of abnormal tracer accumulation in the Prostate and periprostatic tissue. Chapter 7 provides spectrum of skeletal findings on dual-phase 18F-fluoroethylcholine (FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. I have provided quantification data and explained that SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions also exists. Chapter 8 addresses the clinical utility of 18F Choline in the setting of clinical trial in collaboration with Uro-oncology, Nuclear Medicine and Radiology departments. This critical work compares 18F Choline PET-CT and Whole-Body MRI in assessment and decision-making process for salvage treatment of focal radio-recurrent prostate cancer. This chapters concludes that at present WB-MRI cannot be used alone as imaging modality for investigation of biochemical relapse of Prostate Cancer. Chapter 9 is a summary of main findings and discussions from chapters in this thesis. It also highlights the potential applications and future perspectives of novel biomarkers for imaging of prostate cancer

Whole-body imaging of the musculoskeletal system: the value of MR imaging

In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI

A Novel Approach for the Visualisation and Progression Tracking of Metastatic Bone Disease

Metastatic bone disease (MBD) is a common secondary feature of cancer that can cause significant complications, including severe pain and death. Current methods of diagnosis require a highly trained radiologist capable of interpreting medical images and recognising the sites of MBD. These medical images are often noisy, two dimensional, greyscale and usually have a poor resolution. In order to help assist with these issues, several studies have shown that computer aided methods can locate MBD within medical images. However these methods are limited in scope, accuracy, sensitivity, explainability and do not improve upon the poor visualisations of the underlying medical imaging data. To address these limitations, I have developed a novel method of automatic MBD assessment and visualisation using computed tomography (CT) imaging data as the input. The method is fully automated and does not require any human interaction -- although users can interact with a viewer that visualises the results. This method has been tested on CT data from prostate cancer patients as prostate cancer is one of the most common sources of MBD. The method described in this thesis has a sensitivity of 0.871 when detecting sclerotic and lytic lesions within a single data set. This sensitivity is comparable to existing methods, however the scope in detecting these lesions was limited to the vertebrae in previous studies. My method significantly expands this scope to include the ribs, vertebrae, pelvis and proximal femurs. The work in this thesis also provides novel visualisations of the disease and does not suffer from explainability issues that plague modern machine learning algorithms. In addition, I developed a novel method of tracking the spread of MBD at multiple time points using longitudinal CT data. This method is capable of calculating the change in lesion volume size across multiple time points, providing a novel numerical assessment.The Armstrong Trus

Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND METHODS: This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. RESULTS: FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. CONCLUSIONS: FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available

Recurrent Prostate Cancer Diagnostics with 18F-PSMA-1007 PET/CT: A Systematic Review of the Current State

Funding Information: This research was funded by Latvian Council of Science, grant number: lzp-2019/1-0056 “Impact of Targeted Molecular Imaging with 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT in Multimodal Evaluation of Recurrent Prostate Cancer”. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101008571 (PRISMAP). This document reflects only the view of the author(s). The funding agenc(y/ies) is/are not responsible for any use that may be made of the information it contains. Publisher Copyright: © 2022 by the authors.BACKGROUND: Early diagnosis of recurrent prostate cancer is a cornerstone for further adequate therapy planning. Therefore, clinical practice and research still focuses on diagnostic tools that can detect prostate cancer in early recurrence when it is undetectable in conventional diagnostic imaging. 18F-PSMA-1007 PET/CT is a novel method to evaluate patients with biochemical recurrent PCa. The aim of this review was to evaluate the role of 18F-PSMA-1007 PET/CT in prostate cancer local recurrence, lymph node metastases and bone metastases detection. METHODS: Original studies, reviews and five meta-analyses were included in this article. A total of 70 studies were retrieved, 31 were included in the study. RESULTS: All patients described in the studies underwent 18F-PSMA-1007 PET/CT. The administered 18F-PSMA-1007 individual dose ranged from 159 ± 31 MBq to 363.93 ± 69.40 MBq. Results showed that 18F-PSMA-1007 PET/CT demonstrates a good detection rate in recurrent prostate cancer. CONCLUSIONS: 18F-PSMA-1007 PET/CT appears to achieve reliable performance in detecting recurrent prostate cancer. The high detection rate of 18F-PSMA-1007 PET/CT in recurrent prostate cancer was confirmed, especially in local recurrence and small lymph nodes with non-specific characteristics on conventional diagnostic imaging methods. However, several authors emphasize some limitations for this tracer-for example, non-specific uptake in bone lesions that can mimic bone metastases.publishersversionPeer reviewe

Multimodal Partial-Volume Correction: Application to 18F-Fluoride PET/CT Bone Metastases Studies

18F-fluoride PET/CT offers the opportunity for accurate skeletal metastasis staging, compared with conventional imaging methods. 18F-fluoride is a bone-specific tracer whose uptake depends on osteoblastic activity. Because of the resulting increase in bone mineralization and sclerosis, the osteoblastic process can also be detected morphologically in CT images. Although CT is characterized by high resolution, the potential of PET is limited by its lower spatial resolution and the resulting partial-volume effect. In this context, the synergy between PET and CT presents an opportunity to resolve this limitation using a novel multimodal approach called synergistic functional–structural resolution recovery (SFS-RR). Its performance is benchmarked against current resolution recovery technology using the point-spread function (PSF) of the scanner in the reconstruction procedure. Methods: The SFS-RR technique takes advantage of the multiresolution property of the wavelet transform applied to both functional and structural images to create a high-resolution PET image that exploits the structural information of CT. Although the method was originally conceived for PET/MR imaging of brain data, an ad hoc version for whole-body PET/CT is proposed here. Three phantom experiments and 2 datasets of metastatic bone 18F-fluoride PET/CT images from primary prostate and breast cancer were used to test the algorithm performances. The SFS-RR images were compared with the manufacturer’s PSF-based reconstruction using the standardized uptake value (SUV) and the metabolic volume as metrics for quantification. Results: When compared with standard PET images, the phantom experiments showed a bias reduction of 14% in activity and 1.3 cm3 in volume estimates for PSF images and up to 20% and 2.5 cm3 for the SFS-RR images. The SFS-RR images were characterized by a higher recovery coefficient (up to 60%) whereas noise levels remained comparable to those of standard PET. The clinical data showed an increase in the SUV estimates for SFS-RR images up to 34% for peak SUV and 50% for maximum SUV and mean SUV. Images were also characterized by sharper lesion contours and better lesion detectability. Conclusion: The proposed methodology generates PET images with improved quantitative and qualitative properties. Compared with standard methods, SFS-RR provides superior lesion segmentation and quantification, which may result in more accurate tumor characterization

Radiography in Palaeopathology: Where Next?

YesRadiography has frequently been used during palaeopathological research, and plays an important role in the differential diagnosis of many diseases, including Paget¿s disease and carcinomas. Traditionally, radiographs were taken in hospitals with clinical equipment. However industrial radiography techniques have gradually become more commonly used, as their superior image quality and improved potential for diagnoses become recognised. The introduction of radiographic scanners has facilitated the digitisation of these images for dissemination and publication. However this is not all that radiographic digitisation can offer the researcher. Digital image processing (DIP) allows the researcher to focus on an area of interest and to adjust the brightness and contrast of the captured image. This allows the investigation of areas of high radio-opacity and radio-lucency, providing detailed images of the internal structures of bone and pathological lesions undetectable by the naked eye. In addition 3D effects, edge enhancement and sharpening algorithms, available through commonly used image processing software, can be very effective in enhancing the visibility of specific features. This paper will reveal how radiographic digitisation and manipulation can enhance radiographic images of palaeopathological lesions and potentially further our understanding of the bony manifestations of disease