Tumor volume delineation: A pilot study comparing a digital positron-emission tomography prototype with an analog positron-emission tomography system.

We evaluated the potential differences of a digital positron-emission tomography (PET) prototype equipped with photon-counting detectors (D-PET, Philips Healthcare, Cleveland, Ohio, USA) in tumor volume delineation compared with the analog Gemini TF PET system (A-PET, Philips). Eleven oncologic patients first underwent clinical fluorodeoxyglucose (FDG) PET/computed tomography (CT) on A-PET. The D-PET ring was then inserted between the PET and CT scanner of A-PET and the patient was scanned for the second time. Two interpreters reviewed the two sets of PET/CT images for image quality and diagnostic confidence. FDG avid lesions were evaluated for volume measured at 35% and 50% of maximum standard uptake value (SUV) thresholds (35% SUV, 50% SUV), and for SUV gradient as a measure of lesion sharpness. Bland-Altman plots were used to assess the agreement between the two PET scans. Qualitative lesion conspicuity, sharpness, and diagnostic confidence were greater at D-PET than that of A-PET with favorable inter-rater agreements. Median lesion size of the 24 measured lesions was 1.6 cm. The lesion volume at D-PET was smaller at both 35% SUV and 50% SUV thresholds compared with that of A-PET, with a mean difference of - 3680.0 mm3 at 35% SUV and - 835.3 mm3 at 50% SUV. SUV gradient was greater at D-PET than at A-PET by 49.2% (95% confidence interval: 34.1%-60.8%). Given the smaller volume definition, coupled with improved conspicuity and sharpness, digital PET may be more robust and accurate in tumor rendering compared with analog PET not only for radiotherapy planning but also in prognostication and systemic treatment monitoring.

Role of FDG-PET/MRI, FDG-PET/CT, and Dynamic Susceptibility Contrast Perfusion MRI in Differentiating Radiation Necrosis from Tumor Recurrence in Glioblastomas.

BACKGROUND AND PURPOSE: To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). METHODS: The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated. RESULTS: In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r-mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0. CONCLUSION: Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs.

SPECT/CT Detection of a Communicating Arachnoid Cyst in a Patient With Normal Pressure Hydrocephalus.

A 59-year-old man with history of multiple sclerosis and residual sensory and motor dysfunction presented with progressive lower-extremity weakness, ataxic gait, and intermittent urinary incontinence. Brain MRI demonstrated volume loss with disproportionate ventricular dilatation, but no evidence of infarction or abnormal enhancement. Radionuclide cisternography showed early and persistent ventricular reflux, poor progression of radiopharmaceutical over convexities, and delayed clearance in a pattern consistent with normal pressure hydrocephalus. Asymmetric activity in the right parietal region was also identified. Fused SPECT/CT, as well as fusion of the SPECT with a previous brain MRI, demonstrated a communicating arachnoidal cyst.

PET/MRI of the breast.

The future clinical use of the combination of positron emission tomography (PET) with 2-Fluoro[F-18]-2-Deoxy-d-Glucose (FDG)and MRI is still unclear. If a patient requires a PET and breast DCE-MRI for staging purposes, both scans can be done in the same visit. In the breast, DCE-MRI is better at lesion detection (sensitivity), margin evaluation, and has a higher specificity than CT. The potential for multiparametric qualitative and quantitative imaging is also an advantage of PET/MRI which provides opportunity to improve tumor characterization and may ultimately lead to outcome prediction. This review discusses technical and clinical aspects of this emerging technology in breast cancer patients.

Post-treatment PET/CT and p16 status for predicting treatment outcomes in locally advanced head and neck cancer after definitive radiation.

PURPOSE: To retrospectively review post-treatment (post-tx) FDG-PET/CT scans in patients with advanced head and neck squamous cell carcinoma (HNSCC) and known p16 status, treated with definitive (chemo)radiation (RT). METHODS: A total of 108 eligible patients had N2A or greater HNSCC treated with chemoRT from August 1, 2008, to February 28, 2015, with post-tx PET/CT within 6 months after RT. Kaplan-Meier curves, log-rank statistics, and Cox proportional hazards regression were used for statistical analysis. RESULTS: Median follow-up was 2.38 years. Sixty-eight (63.0%) patients had p16+ and 40 (37.0%) had p16- status. Two-year overall survival and recurrence-free survival were 93.4% and 77.8%, respectively. The negative predictive value (NPV) of PET/CT for local recurrence (LR) was 100%. The NPV for regional recurrence (RR) was 96.5% for all patients, 100% for p16+ patients, and 88.5% for p16- patients. The positive predictive value (PPV) of PET/CT for recurrence was 77.3% for all patients, 50.0% for p16+, and 78.6% for p16-. The PPV for LR was 72.7% for all patients, 50.0% for p16+ patients, and 72.7% for p16- patients. The PPV for RR was 50.0% for all patients, 33% for p16+, and 66.6% for p16-. Post-tx PET/CT and p16 status were independent predictors of recurrence-free survival (p < 0.01). CONCLUSIONS: Post-tx PET/CT predicts treatment outcomes in both p16 + and p16- patients, and does so independently of p16 status. P16- patients with negative PET have a 10% risk of nodal recurrence, and closer follow-up in these patients is warranted.

Diagnostic performance of an automated analysis software for the diagnosis of Alzheimer's dementia with 18F FDG PET.

The objective of this study was to assess the ability of a quantitative software-aided approach to improve the diagnostic accuracy of 18F FDG PET for Alzheimer's dementia over visual analysis alone. Twenty normal subjects (M:F-12:8; mean age 80.6 years) and twenty mild AD subjects (M:F-12:8; mean age 70.6 years) with 18F FDG PET scans were obtained from the ADNI database. Three blinded readers interpreted these PET images first using a visual qualitative approach and then using a quantitative software-aided approach. Images were classified on two five-point scales based on normal/abnormal (1-definitely normal; 5-definitely abnormal) and presence of AD (1-definitely not AD; 5-definitely AD). Diagnostic sensitivity, specificity, and accuracy for both approaches were compared based on the aforementioned scales. The sensitivity, specificity, and accuracy for the normal vs. abnormal readings of all readers combined were higher when comparing the software-aided vs. visual approach (sensitivity 0.93 vs. 0.83 P = 0.0466; specificity 0.85 vs. 0.60 P = 0.0005; accuracy 0.89 vs. 0.72 P<0.0001). The specificity and accuracy for absence vs. presence of AD of all readers combined were higher when comparing the software-aided vs. visual approach (specificity 0.90 vs. 0.70 P = 0.0008; accuracy 0.81 vs. 0.72 P = 0.0356). Sensitivities of the software-aided and visual approaches did not differ significantly (0.72 vs. 0.73 P = 0.74). The quantitative software-aided approach appears to improve the performance of 18F FDG PET for the diagnosis of mild AD. It may be helpful for experienced 18F FDG PET readers analyzing challenging cases.

Image Quality and Diagnostic Performance of a Digital PET Prototype in Patients with Oncologic Diseases: Initial Experience and Comparison with Analog PET.

UNLABELLED: We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). METHODS: Twenty-one oncologic patients, mean age 58 y, first underwent clinical (18)F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive (18)F-FDG-avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. RESULTS: The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 ± 0.6), lesion sharpness (4.3 ± 0.6), and diagnostic confidence (3.4 ± 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion-to-blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. CONCLUSION: DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging.

Delayed response in ipilimumab therapy.

Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%. In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial. CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.

Hybrid PET/MR imaging in two sarcoma patients - clinical benefits and implications for future trials.

PET/MRI is an evolving hybrid imaging modality which combines the inherent strengths of MRIs soft-tissue and contrast resolution and PETs functional metabolic capabilities. Bone and soft-tissue sarcoma are a relatively rare tumor entity, relying on MRI for local staging and often on PET/CT for lymph node involvement and metastatic spread evaluation. The purpose of this article is to demonstrate the successful use of PET/MRI in two sarcoma patients. We also use these patients as a starting point to discuss how PET/MRI might be of value in sarcoma. Among its potential benefits are: superior TNM staging than either modality alone, decreased radiation dose, more sensitive and specific follow-up and better assessment of treatment response. These potentials need to be investigated in future PET/MRI soft-tissue sarcoma trials.

Clinical oncologic applications of PET/MRI: a new horizon.

Positron emission tomography/magnetic resonance imaging (PET/MRI) leverages the high soft-tissue contrast and the functional sequences of MR with the molecular information of PET in one single, hybrid imaging technology. This technology, which was recently introduced into the clinical arena in a few medical centers worldwide, provides information about tumor biology and microenvironment. Studies on indirect PET/MRI (use of positron emission tomography/computed tomography (PET/CT) images software fused with MRI images) have already generated interesting preliminary data to pave the ground for potential applications of PET/MRI. These initial data convey that PET/MRI is promising in neuro-oncology and head & neck cancer applications as well as neoplasms in the abdomen and pelvis. The pediatric and young adult oncology population requiring frequent follow-up studies as well as pregnant woman might benefit from PET/MRI due to its lower ionizing radiation dose. The indication and planning of therapeutic interventions and specifically radiation therapy in individual patients could be and to a certain extent are already facilitated by performing PET/MRI. The objective of this article is to discuss potential clinical oncology indications of PET/MRI.

Initial experience of MR/PET in a clinical cancer center.

Magentic Resonance/positron emission tomography (PET) has been introduced recently for imaging of clinical patients. This hybrid imaging technology combines the inherent strengths of MRI with its high soft-tissue contrast and biological sequences with the inherent strengths of PET, enabling imaging of metabolism with a high sensitivity. In this article, we describe the initial experience of MR/PET in a clinical cancer center along with a review of the literature. For establishing MR/PET in a clinical setting, technical challenges, such as attenuation correction and organizational challenges, such as workflow and reimbursement, have to be overcome. The most promising initial results of MR/PET have been achieved in anatomical areas where high soft-tissue and contrast resolution is of benefit. Head and neck cancer and pelvic imaging are potential applications of this hybrid imaging technology. In the pediatric population, MR/PET can decrease the lifetime radiation dose. MR/PET protocols tailored to different types of malignancies need to be developed. After the initial exploration phase, large multicenter trials are warranted to determine clinical indications for this exciting hybrid imaging technology and thereby opening new horizons in molecular imaging.

Utility of SPECT/CT for periparotid sentinel lymph node mapping in the surgical management of head and neck melanoma.

PURPOSE: Sentinel lymph node (SLN) biopsy is instrumental in staging and treatment of cutaneous melanoma. SPECT/CT, single-photon emission computed tomography (SPECT) integrated with computed tomography (CT), increases the accuracy of SLN mapping to improve surgical planning. SPECT/CT can correct for signal scatter to prevent masking, which is especially common in the head and neck. For periparotid lymph nodes SPECT/CT may improve localization of SLNs compared to lymphoscintigraphy. MATERIALS/METHODS: Hospital charts were reviewed for 14 patients with melanoma and suspected lymphatic drainage to the parotid region who received lymphoscintigraphy followed by SPECT/CT prior to surgical excision and SLN. RESULTS: Overall, SPECT/CT provided data, which changed management in 57% of patients. CONCLUSIONS: Fifty-seven percent of our patients benefited from use of SPECT/CT. The distinction between level II and parotid sentinel lymph nodes was clearly identified through SPECT/CT images. We believe that patients with melanoma draining to the parotid region would benefit from SPECT/CT SLN mapping.

Imaging of dedifferentiated papillary thyroid carcinoma with left ventricular metastasis: A rare presentation of papillary thyroid metastatic disease.

Cardiac metastasis in thyroid cancer is extremely rare. Iodine-131-d whole-body scan has been used widely to detect thyroid metastasis. However, in dedifferentiated cases, iodine scan has low diagnostic value particularly for diagnosing cardiac metastasis. In the absence of (131)I uptake, (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) can be used as an alternative and has a high sensitivity for thyroid metastasis, but still low sensitivity for cardiac metastasis. Therefore, meticulous attention to the pattern of uptake and comparison with patients' previous studies is critical. Additionally, cardiac magnetic resonance imaging (MRI) can provide additional and critical information.

Image quality assessment of automatic three-segment MR attenuation correction vs. CT attenuation correction.

The purpose of this study is to systematically evaluate the usefulness of Positron emission tomography/Magnetic resonance imaging (PET/MRI) images in a clinical setting by assessing the image quality of Positron emission tomography (PET) images using a three-segment MR attenuation correction (MRAC) versus the standard CT attenuation correction (CTAC). We prospectively studied 48 patients who had their clinically scheduled FDG-PET/CT followed by an FDG-PET/MRI. Three nuclear radiologists evaluated the image quality of CTAC vs. MRAC using a Likert scale (five-point scale). A two-sided, paired t-test was performed for comparison purposes. The image quality was further assessed by categorizing it as acceptable (equal to 4 and 5 on the five-point Likert scale) or unacceptable (equal to 1, 2, and 3 on the five-point Likert scale) quality using the McNemar test. When assessing the image quality using the Likert scale, one reader observed a significant difference between CTAC and MRAC (p=0.0015), whereas the other readers did not observe a difference (p=0.8924 and p=0.1880, respectively). When performing the grouping analysis, no significant difference was found between CTAC vs. MRAC for any of the readers (p=0.6137 for reader 1, p=1 for reader 2, and p=0.8137 for reader 3). All three readers more often reported artifacts on the MRAC images than on the CTAC images. There was no clinically significant difference in quality between PET images generated on a PET/MRI system and those from a Positron emission tomography/Computed tomography (PET/CT) system. PET images using the automatic three-segmented MR attenuation method provided diagnostic image quality. However, future research regarding the image quality obtained using different MR attenuation based methods is warranted before PET/MRI can be used clinically.

Comparison of standardized uptake values in normal structures between PET/CT and PET/MRI in an oncology patient population.

PURPOSE: The purpose of this study was to compare and correlate standardized uptake values (SUV) derived from magnetic resonance attenuation correction (MRAC) with those derived from computed tomography attenuation correction (CTAC) in an oncology patient population. PROCEDURES: The HIPAA-compliant study was approved by the Internal Review Board and all subjects gave written informed consent prior to inclusion in the study. Forty patients (mean age 61 ± 15.1; 20 male) referred for clinically indicated 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans also underwent a PET/magnetic resonance imaging (MRI) examination. MRAC was performed using an automatic three-segment model. Regions of interest were drawn over eight normal structures in order to obtain SUVmax and SUVmean values. Spearman rank correlation coefficients (r) were calculated and two-tailed paired t tests were performed to compare the SUVmax and SUVmean values obtained from CTAC with those from MRAC. RESULTS: The mean time after FDG injection was 66 ± 7 min for PET/CT and 117 ± 15 min for PET/MRI examination. MRAC SUV values were significantly lower than the CTAC SUV values in mediastinal blood pool (p < 0.001 for both SUVmax and SUVmean) and liver (p = 0.01 for SUVmean). The MRAC SUV values were significantly higher in bone marrow (p < 0.001 for both SUVmax and SUVmean), psoas major muscle (p < 0.001 for SUVmax), and left ventricular myocardium (p < 0.001 for SUVmax and p = 0.01 for SUVmean). For the other normal structures, no significant difference was observed. When comparing SUV values generated from CTAC versus MRAC, high correlations between CTAC and MRAC were observed in myocardium (r = 0.96/0.97 for SUVmax/mean), liver (r = 0.68 for SUVmax), bone marrow (r = 0.80/0.83 for SUVmax/mean), lung tissue (r = 0.70 for SUVmax), and mediastinal blood pool (r = 0.0.68/.069 for SUVmax/mean). Moderate correlations were found in lung tissue (r = 0.67 for SUV mean), liver (r = 0.66 for SUVmean), fat (r = 0.48/0.53 for SUVmax/mean), psoas major muscle (r = 0.54/0.58 for SUVmax/mean), and iliacus muscle (r = 0.41 for SUVmax). Low correlation was found in iliacus muscle (r = 0.32 for SUVmean). CONCLUSIONS: Using the automatic three-segment model, our study showed high correlation for measurement of SUV values obtained from MRAC compared to those from CTAC, as the reference standard. Differences observed between MRAC and CTAC derived SUV values may be attributed to the time-delay between the PET/CT and PET/MRI scans or biologic clearance of radiotracer. Further studies are required to assess SUV measurements when performing different MR attenuation correction techniques.

Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers.

OBJECTIVE: Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. METHODS: We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. RESULTS: 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. CONCLUSIONS: The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

[(18)F]Fluorodeoxyglucose-PET/Computed Tomography, PET, and Magnetic Resonance Imaging: Normal Anatomy, Pitfalls, and Artifacts.

Each anatomic region of the head and neck has physiologic variations that can mimic a primary tumor or lymph node. Many of these variations can be recognized as reflecting benign lymphoid, salivary, brown fat, and muscular activity. A few artifacts are related to computed tomography (CT) attenuation. A knowledge of tumor types and patterns of lymph node and metastatic spread helps categorize patterns as benign or malignant. The anatomic reference of CT helps solve many pitfalls. A recently introduced instrument, PET/magnetic resonance imaging, will face new pitfalls as its role in oncology is developed.

The Application of FDG-PET as Prognostic Indicators in Head and Neck Squamous Cell Carcinoma.

This article discusses the role of FDG-PETederived parameters as prognostic indicators in patients with squamous cell carcinoma of the head and neck. The basic underlying biology of FDG-PET scans and the quantitative information that can be derived are discussed. A review of the literature is performed. Potential applications in the management of head and neck cancer and future directions in clinical trials are discussed.