Whole-Body Multiparametric PET in Clinical Oncology: Current Status, Challenges, and Opportunities.

The interpretation of clinical oncologic PET studies has historically used static reconstructions based on SUVs. SUVs and SUV-based images have important limitations, including dependence on uptake times and reduced conspicuity of tracer-avid lesions in organs with high background uptake. The acquisition of dynamic PET images enables additional PET reconstructions via Patlak modeling, which assumes that a tracer is irreversibly trapped by tissues of interest. The resulting multiparametric PET images capture a tracer's net trapping rate (Ki) and apparent volume of distribution (VD), separating the contributions of bound and free tracer fractions to the PET signal captured in the SUV. Potential benefits of multiparametric PET include higher quantitative stability, superior lesion conspicuity, and greater accuracy for differentiating malignant and benign lesions. However, the imaging protocols necessary for multiparametric PET are inherently more complex and time-intensive, despite the recent introduction of automated or semiautomated scanner-based reconstruction packages. In this Review, we examine the current state of multiparametric PET in whole-body oncologic imaging. We summarize the Patlak methodology and relevant tracer kinetics, discuss clinical workflows and protocol considerations, and highlight clinical challenges and opportunities. We aim to help oncologic imagers make informed decisions about whether to implement multiparametric PET in their clinical practices.

FDG imaging with long-axial field-of-view PET/CT in patients with high blood glucose-a matched pair analysis.

PURPOSE: High blood glucose (hBG) in patients undergoing [18F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations. MATERIALS AND METHODS: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8-11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria. RESULTS: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUVmean, 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUVmax, 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8-11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08). CONCLUSION: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Long-axial field-of-view PET/CT for the assessment of inflammation in calcified coronary artery plaques with [68 Ga]Ga-DOTA-TOC.

PURPOSE: Inflamed, prone-to-rupture coronary plaques are an important cause of myocardial infarction and their early identification is crucial. Atherosclerotic plaques are characterized by overexpression of the type-2 somatostatin receptor (SST2) in activated macrophages. SST2 ligand imaging (e.g. with [68 Ga]Ga-DOTA-TOC) has shown promise in detecting and quantifying the inflammatory activity within atherosclerotic plaques. However, the sensitivity of standard axial field of view (SAFOV) PET scanners may be suboptimal for imaging coronary arteries. Long-axial field of view (LAFOV) PET/CT scanners may help overcome this limitation. We aim to assess the ability of [68 Ga]Ga-DOTA-TOC LAFOV-PET/CT in detecting calcified, SST2 overexpressing coronary artery plaques. METHODS: In this retrospective study, 108 oncological patients underwent [68 Ga]Ga-DOTA-TOC PET/CT on a LAFOV system. [68 Ga]Ga-DOTA-TOC uptake and calcifications in the coronary arteries were evaluated visually and semi-quantitatively. Data on patients' cardiac risk factors and coronary artery calcium score were also collected. Patients were followed up for 21.5 ± 3.4 months. RESULTS: A total of 66 patients (61.1%) presented with calcified coronary artery plaques. Of these, 32 patients had increased [68 Ga]Ga-DOTA-TOC uptake in at least one coronary vessel (TBR: 1.65 ± 0.53). Patients with single-vessel calcifications showed statistically significantly lower uptake (SUVmax 1.10 ± 0.28) compared to patients with two- (SUVmax 1.31 ± 0.29, p < 0.01) or three-vessel calcifications (SUVmax 1.24 ± 0.33, p < 0.01). There was a correlation between coronary artery calcium score (CACS) and [68 Ga]Ga-DOTA-TOC uptake, especially in the LAD (p = 0.02). Stroke and all-cause death occurred more frequently in patients with increased [68 Ga]Ga-DOTA-TOC uptake (15.63% vs. 0%; p:0.001 and 21.88% vs. 6.58%; p: 0.04, respectively) during the follow-up period. CONCLUSION: [68 Ga]Ga-DOTA-TOC as a marker for the macrophage activity can reveal unknown cases of inflamed calcified coronary artery plaques using a LAFOV PET system. [68 Ga]Ga-DOTA-TOC uptake increased with the degree of calcification and correlated with higher risk of stroke and all-cause death. [68 Ga]Ga-DOTA-TOC LAFOV PET/CT may be useful to assess patients' cardiovascular risk.

The clinical acceptability of short versus long duration acquisitions for head and neck cancer using long-axial field-of-view PET/CT: a retrospective evaluation.

PURPOSE: To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. METHODS: HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. RESULTS: A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59-73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). CONCLUSION: In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients.

What Role Does PET/MRI Play in Musculoskeletal Disorders?

Musculoskeletal disorders of nononcological origin are one of the most frequent reasons for consultation. Patients suffering from musculoskeletal disorders also consult more than once for the same reason. This results in multiple clinical follow-ups after several radiological and serum examinations, the main ones including X-rays targeting the painful anatomical region and inflammatory serum parameters. As part of their work up, patients suffering from musculoskeletal disorders often require multisequence, multi-parameter MRI. PET/MRI is a promising imaging modality for their diagnosis, with the added advantage of being able to be performed in a single visit. PET/MRI is particularly useful for diagnosing osteomyelitis, spondylodiscitis, arthritis, many pediatric pathologies, and a wide range of other musculoskeletal pathologies. PET/MRI is already used to diagnose malignant bone tumors such as osteosarcoma. However, current knowledge of the indications for PET/MRI in nononcological musculoskeletal disorders is based on studies involving only a few patients. This review focuses on the usefulness of PET/MRI for diagnosing nononcological musculoskeletal disorders.

Long-axial field-of-view PET/CT: perspectives and review of a revolutionary development in nuclear medicine based on clinical experience in over 7000 patients.

Recently introduced long-axial field-of-view (LAFOV) PET/CT systems represent one of the most significant advancements in nuclear medicine since the advent of multi-modality PET/CT imaging. The higher sensitivity exhibited by such systems allow for reductions in applied activity and short duration scans. However, we consider this to be just one small part of the story: Instead, the ability to image the body in its entirety in a single FOV affords insights which standard FOV systems cannot provide. For example, we now have the ability to capture a wider dynamic range of a tracer by imaging it over multiple half-lives without detrimental image noise, to leverage lower radiopharmaceutical doses by using dual-tracer techniques and with improved quantification. The potential for quantitative dynamic whole-body imaging using abbreviated protocols potentially makes these techniques viable for routine clinical use, transforming PET-reporting from a subjective analysis of semi-quantitative maps of radiopharmaceutical uptake at a single time-point to an accurate and quantitative, non-invasive tool to determine human function and physiology and to explore organ interactions and to perform whole-body systems analysis. This article will share the insights obtained from 2 years' of clinical operation of the first Biograph Vision Quadra (Siemens Healthineers) LAFOV system. It will also survey the current state-of-the-art in PET technology. Several technologies are poised to furnish systems with even greater sensitivity and resolution than current systems, potentially with orders of magnitude higher sensitivity. Current barriers which remain to be surmounted, such as data pipelines, patient throughput and the hindrances to implementing kinetic analysis for routine patient care will also be discussed.

Multiparametric Characterization of Intracranial Gliomas Using Dynamic [18F]FET-PET and Magnetic Resonance Spectroscopy.

Both static and dynamic O-(2-[18F]fluoroethyl)-l-tyrosine-(FET)-PET and 1H magnetic resonance spectroscopy (MRS) are useful tools for grading and prognostication in gliomas. However, little is known about the potential of multimodal imaging comprising both procedures. We therefore acquired NAA/Cr and Cho/Cr ratios in multi-voxel MRS as well as FET-PET parameters in 67 glioma patients and determined multiparametric parameter combinations. Using receiver operating characteristics, differentiation between low-grade and high-grade glioma was possible by static FET-PET (area under the curve (AUC) 0.86, p = 0.001), time-to-peak (TTP; AUC 0.79, p = 0.049), and using the Cho/Cr ratio (AUC 0.72, p = 0.039), while the multimodal analysis led to improved discrimination with an AUC of 0.97 (p = 0.001). In order to distinguish glioblastoma from non-glioblastoma, MRS (NAA/Cr ratio, AUC 0.66, p = 0.031), and dynamic FET-PET (AUC 0.88, p = 0.001) were superior to static FET imaging. The multimodal analysis increased the accuracy with an AUC of 0.97 (p < 0.001). In the survival analysis, PET parameters, but not spectroscopy, were significantly correlated with overall survival (OS, static PET p = 0.014, TTP p = 0.012), still, the multiparametric analysis, including MRS, was also useful for the prediction of OS (p = 0.002). In conclusion, FET-PET and MRS provide complementary information to better characterize gliomas before therapy, which is particularly interesting with respect to the increasing use of hybrid PET/MRI for brain tumors.

Comparison of CT, MRI, and F-18 FDG PET/CT for initial N-staging of oral squamous cell carcinoma: a cost-effectiveness analysis.

BACKGROUND AND PURPOSE: Treatment of oral squamous cell carcinoma (OSCC) is based on clinical exam, biopsy, and a precise imaging-based TNM-evaluation. A high sensitivity and specificity for magnetic resonance imaging (MRI) and F-18 FDG PET/CT are reported for N-staging. Nevertheless, staging of oral squamous cell carcinoma is most often based on computed tomography (CT) scans. This study aims to evaluate cost-effectiveness of MRI and PET/CT compared to standard of care imaging in initial staging of OSCC within the US Healthcare System. METHODS: A decision model was constructed using quality-adjusted life years (QALYs) and overall costs of different imaging strategies including a CT of the head, neck, and the thorax, MRI of the neck with CT of the thorax, and whole body F-18 FDG PET/CT using Markov transition simulations for different disease states. Input parameters were derived from literature and willingness to pay (WTP) was set to US $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Monte Carlo modeling was used for probabilistic sensitivity analysis. RESULTS: In the base-case scenario, total costs were at US $239,628 for CT, US $240,001 for MRI, and US $239,131 for F-18 FDG PET/CT whereas the model yielded an effectiveness of 5.29 QALYs for CT, 5.30 QALYs for MRI, and 5.32 QALYs for F-18 FDG PET/CT respectively. F-18 FDG PET/CT was the most cost-effective strategy over MRI as well as CT, and MRI was the cost-effective strategy over CT. Deterministic and probabilistic sensitivity analysis showed high robustness of the model with incremental cost effectiveness ratio remaining below US $100,000/QALY for a wide range of variability of input parameters. CONCLUSION: F-18 FDG PET/CT is the most cost-effective strategy in the initial N-staging of OSCC when compared to MRI and CT. Despite less routine use, both whole body PET/CT and MRI are cost-effective modalities in the N-staging of OSCC. Based on these findings, the implementation of PET/CT for initial staging could be suggested to help reduce costs while increasing effectiveness in OSCC.

Predictive value of clinical and 18F-FDG-PET/CT derived imaging parameters in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

Aim of this study was to validate the prognostic impact of clinical parameters and baseline 18F-FDG-PET/CT derived textural features to predict histopathologic response and survival in patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the 18F-FDG-PET-derived parameters metabolic tumor volume (MTV), SUVmax, contrast and busyness were calculated for the primary tumor using a SUV-threshold of 3. The parameter uniformity was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040-0.883; p = 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including SUVmax, MTV, busyness, contrast and uniformity. Using multivariate Cox-regression analysis, the heterogeneity parameters busyness (Hazard Ratio (HR) = 1.424, 95% CI: 1.044-1.943; p = 0.026) and contrast (HR = 6.678, 95% CI: 1.969-22.643; p = 0.002) were independently associated with OS, while no independent association with OS was seen for SUVmax and MTV. In patients with ESCC undergoing nCRT and surgery, baseline 18F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features busyness and contrast were independently associated with OS and should be further investigated.

Textural features in FDG-PET/CT can predict outcome in melanoma patients to treatment with Vemurafenib and Ipililumab.

AIM: Recently, textural parameters assessed in FDG-PET/CT as surrogate marker for tumor heterogeneity have been shown to provide prognostic power. Therefore, we investigated the use of such parameters in FDG-PET/CT examinations before the start of immunotherapy with vemurafenib or ipilimumab in patients with malignant melanoma. METHODS: In this retrospective analysis 26 patients with histologically proven advanced melanoma were included. FGD-PET/CT was performed before the start of treatment either with vemurafenib (n = 9) or ipilimumab (n = 17) and tumors were analyzed for textural parameters as well as conventional PET features. Lesions were classified as responding or not responding following PERCIST criteria. ROC analysis was performed to analyze the predictive power and cut-off values. In addition, the change of maximum SUV of the lesions between pretherapeutic PET/CT and another PET/CT performed about 12 weeks after start of treatment was evaluated and correlated with the pretreatment parameters. RESULTS: In both groups, six textural parameters showed statistically significant predictive power as well as the metabolic tumor volume. In the group treated with vemurafenib eight additional textural parameters as well as the maximum and mean SUV and the TLG showed significance. A statistically significant correlation between the change of maximum SUV in the course of treatment and the pretherapeutic parameters was found in both treatment groups for three textural features. CONCLUSION: In patients with malignant melanoma textural parameters in pretherapeutic FDG-PET/CT examinations seem to have prognostic power for treatment response of immunotherapy with vemurafenib and ipilimumab. This can be an important step towards personalized tumor therapy.

The wavelet power spectrum of perfusion weighted MRI correlates with tumor vascularity in biopsy-proven glioblastoma samples.

BACKGROUND: Wavelet transformed reconstructions of dynamic susceptibility contrast (DSC) MR perfusion (wavelet-MRP) are a new and elegant way of visualizing vascularization. Wavelet-MRP maps yield a clear depiction of hypervascular tumor regions, as recently shown. OBJECTIVE: The aim of this study was to elucidate a possible connection of the wavelet-MRP power spectrum in glioblastoma (GBM) with local vascularity and cell proliferation. METHODS: For this IRB-approved study 12 patients (63.0+/-14.9y; 7m) with histologically confirmed IDH-wildtype GBM were included. Target regions for biopsies were prospectively marked on tumor regions as seen on preoperative 3T MRI. During subsequent neurosurgical tumor resection 43 targeted biopsies were taken from these target regions, of which all 27 matching samples were analyzed. All specimens were immunohistochemically analyzed for endothelial cell marker CD31 and proliferation marker Ki67 and correlated to the wavelet-MRP power spectrum as derived from DSC perfusion weighted imaging. RESULTS: There was a strong correlation between wavelet-MRP power spectrum (median = 4.41) and conventional relative cerebral blood volume (median = 5.97 ml/100g) in Spearman's rank-order correlation (κ = .83, p < .05). In a logistic regression model, the wavelet-MRP power spectrum showed a significant correlation to CD31 dichotomized to no or present staining (p = .04), while rCBV did not show a significant correlation to CD31 (p = .30). No significant association between Ki67 and rCBV or wavelet-MRP was found (p = .62 and p = .70, respectively). CONCLUSION: The wavelet-MRP power spectrum derived from existing DSC-MRI data might be a promising new surrogate for tumor vascularity in GBM.

18F-Fluoroethyl-tyrosine uptake is correlated with amino acid transport and neovascularization in treatment-naive glioblastomas.

PURPOSE: To investigate the in vivo correlation between 18F-fluoroethyl-tyrosine (18F-FET) uptake and amino acid transporter expression and vascularization in treatment-naive glioblastomas. METHODS: A total of 43 stereotactic biopsies were obtained from 13 patients with suspected glioblastoma prior to therapy. All patients underwent a dynamic 18F-FET PET/MRI scan before biopsy. Immunohistochemistry was performed using antibodies against SLC7A5 (amino acid transporter), MIB-1 (Ki67, proliferation), CD31 (vascularization) and CA-IX (hypoxia). The intensity of staining was correlated with 18F-FET uptake and the dynamic 18F-FET uptake slope at the biopsy target point. RESULTS: In all patients, the final diagnosis was IDH-wildtype glioblastoma, WHO grade IV. Static 18F-FET uptake was significantly correlated with SLC7A5 staining (r = 0.494, p = 0.001). While the dynamic 18F-FET uptake slope did not show a significant correlation with amino acid transporter expression, it was significantly correlated with the number of CD31-positive vessels (r = -0.350, p = 0.031), which is line with earlier results linking 18F-FET kinetics with vascularization and perfusion. Besides, static 18F-FET uptake also showed correlations with CA-IX staining (r = 0.394, p = 0.009) and CD31 positivity (r = 0.410, p = 0.006). While the correlation between static 18F-FET uptake and SLC7A5 staining was confirmed as significant in multivariate analysis, this was not the case for the correlation with CD31 positivity, most likely because of the lower effect size and the relatively low number of samples. No significant correlation between 18F-FET uptake and Ki67 proliferation index was observed in our cohort. CONCLUSION: Our results support the findings of preclinical studies suggesting that specific 18F-FET uptake in glioblastomas is mediated by amino acid transporters. As proposed previously, dynamic 18F-FET parameters might be more influenced by perfusion and therefore related to properties of the tumour neovascularization.

Personalized Radiotherapy Design for Glioblastoma: Integrating Mathematical Tumor Models, Multimodal Scans, and Bayesian Inference.

Glioblastoma (GBM) is a highly invasive brain tumor, whose cells infiltrate surrounding normal brain tissue beyond the lesion outlines visible in the current medical scans. These infiltrative cells are treated mainly by radiotherapy. Existing radiotherapy plans for brain tumors derive from population studies and scarcely account for patient-specific conditions. Here, we provide a Bayesian machine learning framework for the rational design of improved, personalized radiotherapy plans using mathematical modeling and patient multimodal medical scans. Our method, for the first time, integrates complementary information from high-resolution MRI scans and highly specific FET-PET metabolic maps to infer tumor cell density in GBM patients. The Bayesian framework quantifies imaging and modeling uncertainties and predicts patient-specific tumor cell density with credible intervals. The proposed methodology relies only on data acquired at a single time point and, thus, is applicable to standard clinical settings. An initial clinical population study shows that the radiotherapy plans generated from the inferred tumor cell infiltration maps spare more healthy tissue thereby reducing radiation toxicity while yielding comparable accuracy with standard radiotherapy protocols. Moreover, the inferred regions of high tumor cell densities coincide with the tumor radioresistant areas, providing guidance for personalized dose-escalation. The proposed integration of multimodal scans and mathematical modeling provides a robust, non-invasive tool to assist personalized radiotherapy design.

Combining multimodal imaging and treatment features improves machine learning-based prognostic assessment in patients with glioblastoma multiforme.

BACKGROUND: For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients' overall survival (OS) and progression-free survival (PFS) on the basis of clinical, pathological, semantic MRI-based, and FET-PET/CT-derived information. Finally, the value of adding treatment features was evaluated. METHODS: One hundred and eighty-nine patients were retrospectively analyzed. We assessed clinical, pathological, and treatment information. The VASARI set of semantic imaging features was determined on MRIs. Metabolic information was retained from preoperative FET-PET/CT images. We generated multiple random survival forest prediction models on a patient training set and performed internal validation. Single feature class models were created including "clinical," "pathological," "MRI-based," and "FET-PET/CT-based" models, as well as combinations. Treatment features were combined with all other features. RESULTS: Of all single feature class models, the MRI-based model had the highest prediction performance on the validation set for OS (C-index: 0.61 [95% confidence interval: 0.51-0.72]) and PFS (C-index: 0.61 [0.50-0.72]). The combination of all features did increase performance above all single feature class models up to C-indices of 0.70 (0.59-0.84) and 0.68 (0.57-0.78) for OS and PFS, respectively. Adding treatment information further increased prognostic performance up to C-indices of 0.73 (0.62-0.84) and 0.71 (0.60-0.81) on the validation set for OS and PFS, respectively, allowing significant stratification of patient groups for OS. CONCLUSIONS: MRI-based features were the most relevant feature class for prognostic assessment. Combining clinical, pathological, and imaging information increased predictive power for OS and PFS. A further increase was achieved by adding treatment features.

Consistency of normalized cerebral blood volume values in glioblastoma using different leakage correction algorithms on dynamic susceptibility contrast magnetic resonance imaging data without and with preload.

BACKGROUND AND PURPOSE: Several leakage correction algorithms for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI)-based cerebral blood volume (CBV) measurement have been proposed, and combination with a preload of contrast agent is generally recommended. A single bolus application scheme would largely simplify and facilitate standardized clinical applications, while reducing contrast agent (CA) dose. The aim of this study was, therefore, to investigate whether appropriate leakage correction redundantizes prebolus application by comparing normalized DSC-based CBV (nCBV) measures of two consecutive CA boli. MATERIALS AND METHODS: Twenty-seven patients with suspected glioblastoma (WHO-grade-IV) underwent DSC-MRI during two consecutive boli of Gd-based CA. Four variants of two post-processing leakage correction techniques were compared with respect to nCBV in contrast enhancing tumor tissue. First, a reference curve approach with first pass and full integration of corrected ΔR2*(t), and second, a deconvolution-based approach using singular value decomposition (SVD) with a standard noise-dependent cutoff or Tikhonov regularization. RESULTS: Compared to respective uncorrected values, all leakage correction techniques increased nCBV for data acquired without prebolus, while there was no consistent trend for data acquired with prebolus. The best agreement between corrected nCBV values in contrast enhancing tumor, obtained in the same patients without and with prebolus, respectively, was obtained for the reference curve-based correction approach with either first pass or full integration. CONCLUSION: The reference curve-based leakage correction approach with integration-based nCBV calculation yielded a high accordance between nCBV values without and with prebolus, respectively. Thus, it appears possible to obtain valid nCBV in glioblastoma with a single CA injection.

Can Early Postoperative O-(2-18FFluoroethyl)-l-Tyrosine Positron Emission Tomography After Resection of Glioblastoma Predict the Location of Later Tumor Recurrence?

OBJECTIVE: Glioblastoma inevitably recurs despite aggressive therapy. Therefore, it would be helpful to predict the location of tumor recurrence from postoperative imaging to customize further treatment. O-(2-18Ffluoroethyl)-l-tyrosine (FET) positron emission tomography (PET) might be a helpful technique, because tumor tissue can be differentiated from normal brain tissue with high specificity. METHODS: Thirty-two consecutive patients with perioperative and follow-up imaging data available were included. On postoperative FET-PET, the tumor/normal brain (TTB) ratio around the resection cavity borders was measured. Increased TTB ratios were recorded and anatomically correlated with the site of later tumor recurrence. On postoperative magnetic resonance imaging (MRI), residual contrast-enhancing tumor correlated with the site of later tumor recurrence. RESULTS: Location of progression was predictable using MRI alone in 42% of patients by residual tumor on postoperative MRI. FET-PET was predictive in 25 patients by a clear hot spot at the site of later tumor recurrence. In 3 patients, it was partially predictive and in 4 was not predictive of the tumor recurrence location. One patient without any tracer uptake was recurrence free at the last follow-up examination. In contrast to the postoperative MRI results, tumor recurrence was found in 79% at a site of elevated TTB ratio on postoperative FET-PET. Therefore, the predictability of the tumor recurrence location using postoperative FET-PET was greater than that with MRI, and all cases predictable using MRI could have been predicted using FET-PET. CONCLUSIONS: Postoperative FET-PET can be helpful for planning subsequent therapy, such as repeat resection or radiotherapy, because tumor recurrence can be predicted with relatively greater sensitivity than with MRI alone.

Diagnosis of glioma recurrence using multiparametric dynamic 18F-fluoroethyl-tyrosine PET-MRI.

OBJECTIVES: To investigate the value of combined 18F-fluorethyltyrosine-(FET)-PET/MRI for differentiation between recurrence and treatment-related changes in glioma patients. METHODS: 63 lesions suggestive of recurrence in 47 glioma patients were retrospectively identified. All patients had a dynamic FET scan, as well as morphologic MRI, PWI and DWI on a hybrid PET/MRI scanner. Lesions suggestive of recurrence were marked. ROC analysis was performed univariately and on parameter combination. RESULTS: 50 lesions were classified as recurrence, 13 as radiation necrosis. Diagnosis was based on histology in 23 and follow-up imaging in 40 cases. Sensitivities and specificities for static PET were 80 and 85%, 66% and 77% for PWI, 62 and 77% for DWI and 64 and 79% for PET time-to-peak. AUC was 0.86 (p < 0.001) for static PET, 0.73 (p = 0.013) for PWI, 0.70 (p = 0.030) for DWI and 0.73 (p < 0.001) for dynamic PET. Multiparametric analysis resulted in an AUC of 0.89, notably yielding sensitivity of 76% vs. 56% for PET alone at 100% specificity. CONCLUSION: Simultaneous dynamic FET-PET/MRI was reliably feasible for imaging of recurrent glioma. While all modalities were able to discriminate between recurrence and treatment-related changes, multiparametric analysis added value especially when high specificity was demanded.