Eugene J. Teoh

Phantom and Clinical Evaluation of the Bayesian Penalized Likelihood Reconstruction Algorithm Q.Clear on an LYSO PET/CT System

Q.Clear, a Bayesian penalized-likelihood reconstruction algorithm for PET, was recently introduced by GE Healthcare on their PET scanners to improve clinical image quality and quantification. In this work, we determined the optimum penalization factor (beta) for clinical use of Q.Clear and compared Q.Clear with standard PET reconstructions. Methods: A National Electrical Manufacturers Association image-quality phantom was scanned on a time-of-flight PET/CT scanner and reconstructed using ordered-subset expectation maximization (OSEM), OSEM with point-spread function (PSF) modeling, and the Q.Clear algorithm (which also includes PSF modeling). Q.Clear was investigated for β (B) values of 100–1,000. Contrast recovery (CR) and background variability (BV) were measured from 3 repeated scans, reconstructed with the different algorithms. Fifteen oncology body 18F-FDG PET/CT scans were reconstructed using OSEM, OSEM PSF, and Q.Clear using B values of 200, 300, 400, and 500. These were visually analyzed by 2 scorers and scored by rank against a panel of parameters (overall image quality; background liver, mediastinum, and marrow image quality; noise level; and lesion detectability). Results: As β is increased, the CR and BV decreases; Q.Clear generally gives a higher CR and lower BV than OSEM. For the smallest sphere reconstructed with Q.Clear B400, CR is 28.4% and BV 4.2%, with corresponding values for OSEM of 24.7% and 5.0%. For the largest hot sphere, Q.Clear B400 yields a CR of 75.2% and a BV of 3.8%, with corresponding values for OSEM of 64.4% and 4.0%. Scorer 1 and 2 ranked B400 as the preferred reconstruction in 13 of 15 (87%) and 10 of 15 (73%) cases. The least preferred reconstruction was OSEM PSF in all cases. In most cases, lesion detectability was highest ranked for B200, in 9 of 15 (67%) and 10 of 15 (73%), with OSEM PSF ranked lowest. Poor lesion detectability on OSEM PSF was seen in cases of mildly 18F-FDG–avid mediastinal nodes in lung cancer and small liver metastases due to background noise. Conversely, OSEM PSF was ranked second highest for lesion detectability in most pulmonary nodule evaluation cases. The combined scores confirmed B400 to be the preferred reconstruction. Conclusion: Our phantom measurement results demonstrate improved CR and reduced BV when using Q.Clear instead of OSEM. A β value of 400 is recommended for oncology body PET/CT using Q.Clear.

Novel penalised likelihood reconstruction of PET in the assessment of histologically verified small pulmonary nodules

AbstractObjectivesInvestigate the effect of a novel Bayesian penalised likelihood (BPL) reconstruction algorithm on analysis of pulmonary nodules examined with 18F-FDG PET/CT, and to determine its effect on small, sub-10-mm nodules.Methods18F-FDG PET/CTs performed for nodule evaluation in 104 patients (121 nodules) were retrospectively reconstructed using the new algorithm, and compared to time-of-flight ordered subset expectation maximisation (OSEM) reconstruction. Nodule and background parameters were analysed semi-quantitatively and visually.ResultsBPL compared to OSEM resulted in statistically significant increases in nodule SUVmax (mean 5.3 to 8.1, pu2009<u20090.00001), signal-to-background (mean 3.6 to 5.3, pu2009<u20090.00001) and signal-to-noise (mean 24 to 41, pu2009<u20090.00001). Mean percentage increase in SUVmax (%ΔSUVmax) was significantly higher in nodules ≤10xa0mm (nu2009=u200931, mean 73xa0%) compared to >10xa0mm (nu2009=u200990, mean 42xa0%) (pu2009=u20090.025). Increase in signal-to-noise was higher in nodules ≤10xa0mm (224xa0%, mean 12 to 27) compared to >10xa0mm (165xa0%, mean 28 to 46). Whenxa0applying optimum SUVmax thresholds for detecting malignancy, thexa0sensitivity and accuracy increased using BPL, with the greatest improvements in nodules ≤10xa0mm.ConclusionBPL results in a significant increase in signal-to-background and signal-to-noise compared to OSEM. When semi-quantitative analyses to diagnose malignancy are applied, higher SUVmax thresholds may be warranted owing to the SUVmax increase compared to OSEM.Key Points• Novel Bayesian penalised likelihood PET reconstruction was applied for lung nodule evaluation.n • This was compared to current standard of care OSEM reconstruction.n • The novel reconstruction generated significant increases in lung nodule signal-to-background and signal-to-noise.n • These increases were highest in small, sub-10-mm pulmonary nodules.n • Higher SUVmaxthresholds may be warranted when using semi-quantitative analyses to diagnose malignancy.

Does a novel penalized likelihood reconstruction of 18F-FDG PET-CT improve signal-to-background in colorectal liver metastases?

PURPOSEnIterative reconstruction algorithms are widely used to reconstruct positron emission tomography computerised tomography (PET/CT) data. Lesion detection in the liver by 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) is hindered by 18F-FDG uptake in background liver parenchyma. The aim of this study was to compare semi-quantitative parameters of histologically-proven colorectal liver metastases detected by 18F-FDG-PET/CT using data based on a Bayesian penalised likelihood (BPL) reconstruction, with data based on a conventional time-of-flight (ToF) ordered subsets expectation maximisation (OSEM) reconstruction.nnnMETHODSnA BPL reconstruction algorithm was used to retrospectively reconstruct sinogram PET data. This data was compared with OSEM reconstructions. A volume of interest was placed within normal background liver parenchyma. Lesions were segmented using automated thresholding. Lesion maximum standardised uptake value (SUVmax), standard deviation of background liver parenchyma SUV, signal-to-background ratio (SBR), and signal-to-noise ratio (SNR) were collated. Data was analysed using paired Students t-tests and the Pearson correlation.nnnRESULTSnForty-two liver metastases from twenty-four patients were included in the analysis. The average lesion SUVmax increased from 8.8 to 11.6 (p<0.001) after application of the BPL algorithm, with no significant difference in background noise. SBR increased from 4.0 to 4.9 (p<0.001) and SNR increased from 10.6 to 13.1 (p<0.001) using BPL. There was a statistically significant negative correlation between lesion size and the percentage increase in lesion SUVmax (p=0.03).nnnCONCLUSIONSnThis BPL reconstruction algorithm improved SNR and SBR for colorectal liver metastases detected by 18F-FDG-PET/CT, increasing the lesion SUVmax without increasing background liver SUV or image noise. This may improve the detection of FDG-avid focal liver lesions and the diagnostic performance of clinical 18F-FDG-PET/CT in this setting, with the largest impact for small foci.

Restaging oesophageal cancer after neoadjuvant therapy with 18 F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery

AbstractObjectivesIt is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk.MethodsThis was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by 18F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014).ResultsThree hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91xa0%) and PET-CT in 17 (6.07xa0%). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1xa0%). PET-CT was more sensitive than CT (pu2009=u20090.005, McNemar’s test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0xa0%; both risk factors), medium (22.4xa0%; either), and low risk (3.87xa0%; neither) groups (pu2009<u20090.001). Decision theory supported restaging PET-CT.ConclusionsPET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply.Key Points• Restaging18F-FDG-PET-CT after neoadjuvant chemotherapy identifies metastases in 6xa0% of patientsn • Restaging18F-FDG-PET-CT is more sensitive than CT for detecting interval progressionn • Despite this, at surgery 10xa0% of patients had unsuspected incurable diseasen • New concepts (FDG-avid nodal stage and response) plus tumour impassability stratify riskn • Higher risk (if not all) patients may benefit from additional restaging modalities

18F-FDG PET/CT assessment of histopathologically confirmed mediastinal lymph nodes in non-small cell lung cancer using a penalised likelihood reconstruction

PurposeTo investigate whether using a Bayesian penalised likelihood reconstruction (BPL) improves signal-to-background (SBR), signal-to-noise (SNR) and SUVmax when evaluating mediastinal nodal disease in non-small cell lung cancer (NSCLC) compared to ordered subset expectation maximum (OSEM) reconstruction.Materials and methods18F-FDG PET/CT scans for NSCLC staging in 47 patients (112 nodal stations with histopathological confirmation) were reconstructed using BPL and compared to OSEM. Node and multiple background SUV parameters were analysed semi-quantitatively and visually.ResultsComparing BPL to OSEM, there were significant increases in SUVmax (mean 3.2–4.0, p<0.0001), SBR (mean 2.2–2.6, p<0.0001) and SNR (mean 27.7–40.9, p<0.0001). Mean background SNR on OSEM was 10.4 (range 7.6–14.0), increasing to 12.4 (range 8.2–16.7, p<0.0001). Changes in background SUVs were minimal (largest mean difference 0.17 for liver SUVmean, p<0.001). There was no significant difference between either algorithm on receiver operating characteristic analysis (p=0.26), although on visual analysis, there was an increase in sensitivity and small decrease in specificity and accuracy on BPL.ConclusionBPL increases SBR, SNR and SUVmax of mediastinal nodes in NSCLC compared to OSEM, but did not improve the accuracy for determining nodal involvement.Key Points• Penalised likelihood PET reconstruction was applied for assessing mediastinal nodes in NSCLC.• The new reconstruction generated significant increases in signal-to-background, signal-to-noise and SUVmax.• This led to an improvement in visual sensitivity using the new algorithm.• Higher SUVmaxthresholds may be appropriate for semi-quantitative analyses with penalised likelihood.

Mycotic aneurysm of the superior mesenteric artery and other sequelae of prosthetic valve endocarditis on 18F-FDG PET/CT

A 61-year-old man with an implantable cardioverter defibrillator (ICD) and treated tissue aortic valve Staphylococcus epidermidis endocarditis, re-presented with fevers. Echocardiography confirmed recurrent valvular vegetations and blood cultures grew S. epidermidis. F-FDG PET/CT was performed to exclude infection associated with the ICD or elsewhere. This demonstrated a markedly FDG-avid (SUVmax 12.9) dilated proximal superior mesenteric artery (a) surrounded by fat stranding (b), a curvilinear moderately FDG-avid (SUVmax 6.2) normal calibre distal splenic artery (c), confirmed as mycotic thrombus on subsequent CT angiography, and photopenic splenic infarcts (d). There was mild–moderate FDG uptake associated with the prosthetic valve (e) attributed to the vegetations, with no abnormal FDG uptake relating to the ICD. This case illustrates the utility of PET/CT to delineate extracardiac sites of septic embolism and their sequelae [1], and to investigate cardiac device infection (specificities of 85 – 100 %) [2, 3]. The negative finding practically excluded ICD infection and informed decisions on device removal.

PREDICTING PATHOLOGICAL RESPONSE OF ESOPHAGEAL CANCER TO NEOADJUVANT CHEMOTHERAPY: THE IMPLICATIONS OF METABOLIC NODAL RESPONSE FOR PERSONALISED THERAPY

Only a minority of esophageal cancers demonstrates a pathologic tumor response (pTR) to neoadjuvant chemotherapy (NAC). 18F-FDG PET/CT is often used for restaging after NAC and to assess response. Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR, using avidity of the primary tumor alone. However, definitions of such metabolic tumor response (mTR) vary. We aimed to comprehensively reevaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and metabolic nodal response (mNR). Methods: This was a single-center retrospective U.K. cohort study. All patients with esophageal cancer staged before NAC with PET/CT and after with CT or PET/CT and undergoing resection from 2006 to 2014 were identified. pTR was defined as Mandard tumor regression grade 1–3; imaging parameters included metrics of tumor avidity (SUVmax/mean/peak), composites of avidity and volume (including metabolic tumor volume), nodal SUVmax, and our new concepts of mN stage and mNR. Results: Eighty-two (27.2%) of 301 patients demonstrated pTR. No pre-NAC PET parameters predicted pTR. In 220 patients restaged by PET/CT, the optimal tumor ΔSUVmax threshold was a 77.8% reduction. This was as sensitive as the current PERCIST 30% reduction, but more specific with a higher negative predictive value (P < 0.001). ΔSUVmax and Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Although both mTR and mNR were associated with pTR, in 82 patients with 18F-FDG–avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR. Conclusion: Current definitions of metabolic response are suboptimal and too simplistic. Composite avidity/volume measures improve prediction. mNR may further improve response assessment, by specifically assessing metastatic tumor subpopulations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone.

Crossed cerebellar diaschisis due to cerebral diffuse large B cell lymphoma on 18F-FDG PET/CT

A 55-year-old male with a history of diffuse large B cell lymphoma (DLBCL) presented with right-arm weakness, expressive dysphasia, and left Horner’s syndrome. CT brain demonstrated multiple left supratentorial masses, and involvement including the left midbrain (Fig. 1a). Disease recurrence was diagnosed following stereotactic biopsy. 18F-FDG PET/CT of the whole body 2 weeks post-biopsy for complete staging demonstrated the masses to be markedly FDG-avid, with the most FDG-avid focus within the left midbrain (Fig. 1b, SUVmax = 19.4). No active extracranial disease was demonstrated. There was a mild generalised reduction in metabolism throughout the left cerebral grey matter compared to the right, with reduced FDG uptake throughout the contralateral cerebellar hemisphere (Fig. 1c, d, coronal images) in keeping with crossed cerebellar diaschisis (CCD). In a separate case, a 60-year-old female presented with ataxia and peripheral visual field defects. CT brain demonstrated multiple right-sided intra-cerebral masses, and involvement including the thalamus (Fig. 2a). Subsequent biopsy confirmed cerebral DLBCL. 18F-FDG PET/CT demonstrated the right supratentorial disease to be extremely FDG-avid (Fig. 2b, SUVmax = 35.2) with no extracranial disease. There was reduced metabolism in the right middle and posterior cerebral artery territories (Fig. 2c) with corresponding reduction of FDG uptake in the left cerebellar hemisphere (Fig. 2d) in keeping with CCD. CCD is a phenomenon of hypometabolism within the cerebellar hemisphere contralateral to the supratentorial pathology, and was first described in cerebral infarction. In addition to ischaemia, CCD has also been described in epilepsy and primary brain tumours. This is considered to be due to transneuronal depression mediated by the corticopontocerebellar pathway. These two cases illustrate that CCD can also be a manifestation of cerebral lymphoma, which has not been previously described in the peerreviewed literature. Since most lymphoma staging 18F-FDG PET/CT scans are performed from either mid-skull or skull base, the presence of asymmetric uptake within the cerebellar hemispheres should prompt further brain imaging to evaluate for cerebral involvement. As with the latter case, CCD should be considered in the subset of patients where supratentorial disease cannot otherwise account for persistent cerebellar symptoms. Structural imaging of the posterior fossa will usually be normal in CCD, justifying a heightened awareness of this phenomenon amongst physicians and radiologists.

Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer

Summary Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect.

Bayesian penalised likelihood reconstruction (Q.Clear) of 18F-fluciclovine PET for imaging of recurrent prostate cancer: semi-quantitative and clinical evaluation

Objective: 18F-Fluciclovine (FACBC) is an amino acid PET radiotracer approved for recurrent prostate cancer imaging. We investigate the use of Bayesian penalised likelihood (BPL) reconstruction for 18F-fluciclovine PET. Methods: 15 18F-fluciclovine scans were reconstructed using ordered subset expectation maximisation (OSEM), OSEM + pointu2009spread function (PSF) modelling and BPL using β-values 100–600. Lesion maximum standardised uptake value (SUVmax), organ SUVmean and standard deviation were measured. Deidentified reconstructions (OSEM, PSF, BPL using β200–600) from 10 cases were visually analysed by two readers who indicated their most and least preferred reconstructions, and scored overall image quality, noise level, background marrow image quality and lesion conspicuity. Results: Comparing BPL to OSEM, there were significant increments in lesion SUVmax and signal-to-background up to β400, with highest gain in β100 reconstructions (mean ΔSUVmax 3.9, p < 0.0001). Organ noise levels increased on PSF, β100 and β200 reconstructions. Across BPL reconstructions, there was incremental reduction in organ noise with increasing β, statistically significant beyond β300–500 (organ-dependent). Comparing with OSEM and PSF, lesion signal-to-noise was significantly increased in BPL reconstructions where β ≥ 300u2009and ≥ 200u2009respectively. On visual analysis, β 300 had the first and second highest scores for image quality, β500 and β600 equal highest scores for marrow image quality and least noise, PSF and β 200 had first and second highest scores for lesion conspicuity. For overall preference, one reader preferred β 300 in 9/10 cases and the other preferred β 200 in all cases. Conclusion: BPL reconstruction of 18F-fluciclovine PET images improves signal-to-noise ratio, affirmed by overall reader preferences. On balance, β300 is suggested for 18F-fluciclovine whole body PET image reconstruction using BPL. Advances in knowledge: The optimum β is different to that previously published for 18F-fluorodeoxyglucose, and has practical implications for a relatively new tracer in an environment with modern reconstruction technologies.