Evaluation of positron emission tomographic tracers for imaging of papillomavirus-induced tumors in rabbits.

In this study, simultaneous positron emission tomography (PET)/magnetic resonance (MR) imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-d-glucose (18F-FDG), 11C-choline, and 18F-fluorothymidine (18F-FLT) to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.

Navigation system for minimally invasive esophagectomy: experimental study in a porcine model.

BACKGROUND: Navigation systems potentially facilitate minimally invasive esophagectomy and improve patient outcome by improving intraoperative orientation, position estimation of instruments, and identification of lymph nodes and resection margins. The authors' self-developed navigation system is highly accurate in static environments. This study aimed to test the overall accuracy of the navigation system in a realistic operating room scenario and to identify the different sources of error altering accuracy. METHODS: To simulate a realistic environment, a porcine model (n = 5) was used with endoscopic clips in the esophagus as navigation targets. Computed tomography imaging was followed by image segmentation and target definition with the medical imaging interaction toolkit software. Optical tracking was used for registration and localization of animals and navigation instruments. Intraoperatively, the instrument was displayed relative to segmented organs in real time. The target registration error (TRE) of the navigation system was defined as the distance between the target and the navigation instrument tip. The TRE was measured on skin targets with the animal in the 0° supine and 25° anti-Trendelenburg position and on the esophagus during laparoscopic transhiatal preparation. RESULTS: On skin targets, the TRE was significantly higher in the 25° position, at 14.6 ± 2.7 mm, compared with the 0° position, at 3.2 ± 1.3 mm. The TRE on the esophagus was 11.2 ± 2.4 mm. The main source of error was soft tissue deformation caused by intraoperative positioning, pneumoperitoneum, surgical manipulation, and tissue dissection. CONCLUSION: The navigation system obtained acceptable accuracy with a minimally invasive transhiatal approach to the esophagus in a realistic experimental model. Thus the system has the potential to improve intraoperative orientation, identification of lymph nodes and adequate resection margins, and visualization of risk structures. Compensation methods for soft tissue deformation may lead to an even more accurate navigation system in the future.

Technical performance evaluation of a human brain PET/MRI system.

OBJECTIVES: Technical performance evaluation of a human brain PET/MRI system. METHODS: The magnetic field compatible positron emission tomography (PET) insert is based on avalanche photodiode (APD) arrays coupled with lutetium oxyorthosilicate (LSO) crystals and slip-fits into a slightly modified clinical 3-T MRI system. The mutual interference between the two imaging techniques was minimised by the careful design of the hardware to maintain the quality of the B (0) and B (1) field homogeneity. RESULTS: The signal-to-noise ratio (SNR) and the homogeneity of the MR images were minimally influenced by the presence of the PET. Measurements according to the Function Biomedical Informatics Research Network (FBIRN) protocol proved the combined system's ability to perform functional MRI (fMRI). The performance of the PET insert was evaluated according to the National Electrical Manufacturers Association (NEMA) standard. The noise equivalent count rate (NEC) peaked at 30.7 × 10(3) counts/s at 7.3 kBq/mL. The point source sensitivity was greater than 7 %. The spatial resolution in the centre field of view was less than 3 mm. Patient data sets clearly revealed a noticeably good PET and MR image quality. CONCLUSION: PET and MRI phantom tests and first patient data exhibit the device's potential for simultaneous multiparametric imaging. KEY POINTS: • Combination of PET and MRI is a new emerging imaging technology. • Evaluated brain PET/MRI enables uncompromised imaging performance. • PET/MRI aims to provide multiparametric imaging allowing acquisition of morphology and metabolism.

Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI.

BACKGROUND: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. PURPOSE: To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. MATERIAL AND METHODS: ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 × 128 and 192 × 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. RESULTS: Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51 ± 9 and 51 ± 7 mL/100 g/min for the 128 × 128 and 192 × 192 matrices (stand-alone MR, 57 ± 2 and 55 ± 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 × 192 matrix size (P < 0.01), the relative signal change (δS) was significantly lower for the 192 × 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. CONCLUSION: ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.

Feasibility of simultaneous PET/MR imaging in the head and upper neck area.

OBJECTIVE: The aim of this pilot study was to test and demonstrate the feasibility of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) of the head and upper neck area using a new hybrid PET/MRI system. METHODS: Eight patients with malignant head and neck tumours were included in the pilot study. Directly after routine PET/CT imaging with a whole-body system using the glucose derivative 2-[¹8F]fluoro-2deoxy-D-glucose (FDG) as a radiotracer additional measurements were performed with a prototype PET/MRI system for simultaneous PET and MR imaging. Physiological radiotracer uptake within regular anatomical structures as well as tumour uptake were evaluated visually and semiquantitatively (metabolic ratios) in relation to cerebellar uptake on the PET/MRI and PET/CT systems. RESULTS: The MR datasets showed excellent image quality without any recognisable artefacts caused by the inserted PET system. PET images obtained with the PET/MRI system exhibited better detailed resolution and greater image contrast in comparison to those from the PET/CT system. An excellent agreement between metabolic ratios obtained with both PET systems was found: R = 0.99 for structures with physiological tracer uptake, R = 0.96 for tumours. CONCLUSION: Simultaneous PET/MRI of the head and upper neck area is feasible with the new hybrid PET/MRI prototype.

Resection of the intrapancreatic bile duct preserving the pancreas.

Benign neoplasms of the distal bile duct are rare, but pose a therapeutic challenge. Usually, these lesions are resected by means of ampullectomy if located in close proximity to the ampulla of Vateri or by partial pancreaticoduodenectomy if located intrapancreatic and distant from the ampulla. Here, we present a case of an intrapancreatic benign neuroendocrine tumor that was resected by performing a pancreas-preserving distal bile duct resection. First, a duodenotomy was carried out and a probe was inserted into the pancreatic duct to avoid inadvertent injury. Subsequently, the bile duct was divided proximal the lesion and dissected towards the ampulla. Pancreatic parenchyma was dissected dorsally and closed using absorbable interrupted sutures. The duodenal incision was closed, and reconstruction was performed by an end-to-side hepaticojejunostomy and a Roux-Y jejunojejunostomy. The postoperative course of the patient was uneventful. In conclusion, pancreas-preserving distal bile duct resection might be an option for intrapancreatic benign lesions of the distal bile duct that would otherwise require a partial pancreaticoduodenectomy.

The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic tumor with an innate resistance to therapy. Pancreatic stellate cells (PSCs) produce this excessively desmoplastic microenvironment. The impact of PSC activity on PDAC behavior in vivo is analyzed. METHODS: 233 patients who underwent surgery for PDAC were evaluated by immunohistochemistry using antibodies against alpha-smooth muscle actin as a marker of PSC activity. Aniline was used to stain collagen deposition. The ratio of alpha-smooth muscle actin-stained area to collagen-stained area was defined as the activated stroma index (ASI). Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. RESULTS: Four major patterns of collagen deposition were defined with regard to PSC activity. The combination of high stromal activity and low collagen deposition was associated with a worse prognosis, whereas the combination of high collagen deposition and low stromal activity indicated a better prognosis. Patients with the lowest ASI had the best median survival rate (25.7 mo). The highest ASI was found in patients with the worst median survival rate (16.1 mo; P = .007; lowest vs highest ASI: hazard ratio, 1.61; 95% confidence interval, 1.014-2.562). ASI was an independent prognostic marker in multivariable survival analysis comparable with the nodal status of cancer. CONCLUSIONS: The activated stroma index is a novel independent prognostic marker in PDAC in cases undergoing surgery. This finding highlights the impact of the microenvironment in cancer progression and on patient survival.

Positron emission tomography/magnetic resonance imaging: the next generation of multimodality imaging?

Multimodal imaging is now well-established in routine clinical practice. Especially in the field of nuclear medicine, new positron emission tomography (PET) installations comprise almost exclusively combined PET/computed tomography (CT) scanners rather than PET-only systems. However, PET/CT has certain notable shortcomings, including the inability to perform simultaneous data acquisition and the significant radiation dose to the patient contributed by CT. Magnetic resonance imaging (MRI) offers, compared with CT, better contrast among soft tissues as well as functional-imaging capabilities. Therefore, the combination of PET with MRI provides many advantages that go far beyond simply combining functional PET information with structural MRI information. Many technical challenges, including possible interference between these modalities, have to be solved when combining PET and MRI, and various approaches have been adapted to resolving these issues. Here, we present an overview of current working prototypes of combined PET/MRI scanners from different groups. In addition, besides PET/MRI images of mice, the first such images of a rat acquired with the first commercial clinical PET/MRI scanner, are presented. The combination of PET and MRI is a promising tool in preclinical research and will certainly progress to clinical application.

No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease.

BACKGROUND: As only a minority of alcoholics develop cirrhosis, polymorphic genes, whose products are involved in fibrosis development were suggested to confer individual susceptibility. We tested whether a functional promoter polymorphism in the gene encoding matrix metalloproteinase-3 (MMP-3; 1171 5A/6A) was associated liver cirrhosis in alcoholics. METHODS: Independent cohorts from the UK and Germany were studied. (i) UK cohort: 320 alcoholic cirrhotics and 183 heavy drinkers without liver damage and (ii) German cohort: 149 alcoholic cirrhotics, 220 alcoholic cirrhotics who underwent liver transplantation and 151 alcoholics without liver disease. Patients were genotyped for MMP-3 variants by restriction fragment length polymorphism, single strand confirmation polymorphism, and direct sequencing. In addition, MMP-3 transcript levels were correlated with MMP-3 genotype in normal liver tissues. RESULTS: Matrix metalloproteinase-3 genotype and allele distribution in all 1023 alcoholic patients were in Hardy-Weinberg equilibrium. No significant differences in MMP-3 genotype and allele frequencies were observed either between alcoholics with or without cirrhosis. There were no differences in hepatic mRNA transcription levels according to MMP-3 genotype. CONCLUSIONS: Matrix metalloproteinase-3 1171 promoter polymorphism plays no role in the genetic predisposition for liver cirrhosis in alcoholics. Stringently designed candidate gene association studies are required to exclude chance observations.

Impact of the Arterial Input Function Recording Method on Kinetic Parameters in Small-Animal PET.

The goal of this study was to validate the use of an MR-compatible blood sampler (BS) with a detector system based on a lutetium oxyorthosilicate scintillator and avalanche photodiodes for small-animal PET. Methods: Five rats underwent a 60-min 18F-FDG study. For each animal, the arterial input function (AIF) was derived from the BS recording, from manual sampling (MS), and from the PET image. These AIFs were applied for kinetic modeling of the striatum using the irreversible 2-tissue-compartment model. The MS-based technique with a dispersion correction served as a reference approach, and the kinetic parameters that were estimated with the BS- and the image-derived AIFs were compared with the reference values. Additionally, the effect of applying a population-based activity ratio for plasma to whole blood (p/wb) and the dispersion correction was assessed. Results: The K1, k2, and k3 values estimated with the reference approach were 0.174 ± 0.037 mL/min/cm3, 0.342 ± 0.080 1/min, and 0.048 ± 0.009 1/min, respectively. The corresponding parameters obtained with the BS- and image-derived AIFs deviated from these values by 0.6%-18.8% and 16.7%-47.9%, respectively. To compensate for the error in the BS-based technique, data from one MS collected at the end of the experiment were combined with the data from the first 10 min of the BS recording. This approach reduced the deviation in the kinetic parameters to 1.8%-6.3%. Using p/wb led to a 1.7%-8.3% difference from the reference parameters. The sensitivity of the BS was 23%, the energy resolution for the 511-keV photopeak was 19%, and the timing resolution was 11.2 ns. Conclusion: Online recording of the blood activity level with the BS allows precise measurement of AIF, without loss of blood volume. Combining the BS data with one MS is the most accurate approach for the data analysis. The high sensitivity of the device may allow application of lower radioactivity doses.

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors.

BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling.

Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer.

BACKGROUND: Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. METHODS: A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. RESULTS: In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. CONCLUSION: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients.

A new tool for experimental tumour research.

Surgical resected tumours are often stored for hours in the clinic upon transfer to the bench leading to apoptosis of tumour cells making them no longer suitable for molecular analysis and diagnostic procedures. The way out of this problem may be a new oxygen-enriched solution (OES). We tested this agent using surgical resections of carcinomas of lung, rectum and pancreas. Immediately after resection, one part of each individual tumour was stored in PBS and the other part in OES, and the content of viable or dead cells was determined by trypan blue exclusion and MTT-assay. We found that OES keeps tumour cells up to 3 days and longer more viable than PBS and reduces the percentage of dead cells without inducing therapy resistance and affecting the outcome of experimental procedures. Thus, storing freshly resected tumours in OES may save time for tumour transfer and initiation of experiments.

Shine-Through in PET/MR Imaging: Effects of the Magnetic Field on Positron Range and Subsequent Image Artifacts.

UNLABELLED: Simultaneous PET/MR imaging is an emerging hybrid modality for clinical and preclinical imaging. The static magnetic field of the MR imaging device affects the trajectory of the positrons emitted by the PET radioisotopes. This effect translates into an improvement of the spatial resolution in transaxial images. However, because of the elongation of the positron range distribution along the magnetic field, the axial resolution worsens and shine-through artifacts may appear. These artifacts can lead to misinterpretation and overstaging. The aim of this work was to study the relevance of this effect. METHODS: Measurements were performed in a 3-tesla PET/MR scanner. A 1-cm(2) piece of paper, soaked with a radioisotope and placed in air, was scanned, and the magnitude of the shine-through was quantified from the PET images for various radioisotopes. Additionally, PET/MR and PET/CT images of the lungs and the larynx with trachea of a deceased swine were obtained after injecting a mixture of NiSO4 and (68)Ga to simulate hot tumor lesions. RESULTS: For the radioactive paper, shine-through artifacts appeared in the location of the acrylic glass backplane, located 3 cm from the source in the axial direction. The ratio between the activity of the shine-through and the activity reconstructed in the original location ranged from 0.9 ((18)F) to 5.7 ((68)Ga). For the larynx-with-trachea images, the magnitude of the artifacts depended on the organ orientation with respect to the magnetic field. The shine-through activity could reach 46% of the reconstructed activity (larynx lesion). The lesion within the trachea produced 2 artifacts, symmetrically aligned with the magnetic field and characterized by artifact-to-lesion volume-of-interest ratios ranging from 21% to 30%. CONCLUSION: In simultaneous PET/MR imaging, the effect of the magnetic field on positrons may cause severe artifacts in the PET image when the lesions are close to air cavities and high-energy radioisotopes are used. For accurate staging and interpretation, this effect needs to be recognized and adequate compensation techniques should be developed.

Principles of PET/MR Imaging.

Hybrid PET/MR systems have rapidly progressed from the prototype stage to systems that are increasingly being used in the clinics. This review provides an overview of developments in hybrid PET/MR systems and summarizes the current state of the art in PET/MR instrumentation, correction techniques, and data analysis. The strong magnetic field requires considerable changes in the manner by which PET images are acquired and has led, among others, to the development of new PET detectors, such as silicon photomultipliers. During more than a decade of active PET/MR development, several system designs have been described. The technical background of combined PET/MR systems is explained and related challenges are discussed. The necessity for PET attenuation correction required new methods based on MR data. Therefore, an overview of recent developments in this field is provided. Furthermore, MR-based motion correction techniques for PET are discussed, as integrated PET/MR systems provide a platform for measuring motion with high temporal resolution without additional instrumentation. The MR component in PET/MR systems can provide functional information about disease processes or brain function alongside anatomic images. Against this background, we point out new opportunities for data analysis in this new field of multimodal molecular imaging.

On the quantification accuracy, homogeneity, and stability of simultaneous positron emission tomography/magnetic resonance imaging systems.

OBJECTIVE: A potential major application of simultaneous avalanche photodiode-based positron emission tomography (PET)/magnetic resonance imaging (MRI) systems are quantitative brain studies for cerebral blood flow measurements in combination with blood-oxygen-level-dependent or perfusion MRI, requiring a high performance for both modalities. Thus, we evaluated PET quantification accuracy and homogeneity for 2 different simultaneous PET/MRI systems (whole-body and brain scanner) compared with those of a state-of-the-art PET detector (PET/computed tomography) using phantom studies. In addition, we investigated the long-term stability of PET and quality of functional MRI measurements of a clinical whole-body PET/MRI scanner. MATERIALS AND METHODS: Phantom measurements were conducted using spheres filled with [F]-fluoride distributed in a homogeneous cylinder phantom at different positions inside the PET field of view. Recovery values and standard deviations were extracted from resulting PET images. The influence of magnetic resonance-based attenuation correction and that of activity outside the PET field of view on the recovery values of these spheres was evaluated. Furthermore, long-term PET stability of the whole-body PET/MRI system was assessed by evaluating position profiles, energy spectra, count rates, and recovery values from [Ge]-phantom scans. Functional MRI applicability was tested in accordance with the functional Biomedical Information Research Network procedure. RESULTS: The BrainPET system showed high recovery values (up to 99%) but also increased variability (up to 7.4%). Significant underestimations in PET quantification near activity outside the PET field of view were found (up to 80%). Using magnetic resonance-based attenuation correction led to an underestimation in PET activity of approximately 7%. In distinction, the whole-body PET/MRI system revealed performance similar to the PET/computed tomographic scanner (recovery values up to approximately 60% with a variability of approximately 4%). Long-term stability and fMRI performance of the whole-body PET/MRI scanner showed no degradation compared with stand-alone systems. CONCLUSIONS: Homogeneity and accuracy of avalanche photodiode-based PET detectors is comparable with those of the state-of-the-art detectors based on photomultiplier tubes. However, attenuation correction on PET/MRI systems has to be adapted carefully for quantitative PET measurements. The BrainPET system needs improved scatter correction to perform quantitative brain studies. The whole-body PET/MRI scanner, however, is applicable for quantitative brain studies.

Physics and applications of positron beams in an integrated PET/MR.

In PET/MR systems having the PET component within the uniform magnetic field interior to the MR, positron beams can be injected into the PET field of view (FOV) from unshielded emission sources external to it, as a consequence of the action of the Lorentz force on the transverse components of the positron's velocity. Such beams may be as small as a few millimeters in diameter, but extend 50 cm or more axially without appreciable divergence. Larger beams form 'phantoms' of annihilations in air that can be easily imaged, and that are essentially free of γ-ray attenuation and scatter effects, providing a unique tool for characterizing PET systems and reconstruction algorithms. Thin targets intersecting these beams can produce intense annihilation sources having the thickness of a sheet of paper, which are very useful for high resolution measurements, and difficult to achieve with conventional sources. Targeted beams can provide other point, line and surface sources for various applications, all without the need to have radioactivity within the FOV. In this paper we discuss the physical characteristics of positron beams in air and present examples of their applications.

Imaging findings and therapy response monitoring in chronic sclerodermatous graft-versus-host disease: preliminary data of a simultaneous PET/MRI approach.

PURPOSE: Our objective was a multifunctional imaging approach of chronic sclerodermatous graft-versus-host disease (ScGVHD) and its course during therapy using PET/MRI. METHODS: We performed partial-body PET/CT and PET/MRI of the calf in 6 consecutively recruited patients presenting with severe ScGVHD. The patients were treated with different immunosuppressive regimens and supportive therapies. PET/CT scanning started 60.5 ± 3.3 minutes, PET/MRI imaging 139.5 ± 16.7 minutes after (18)F-FDG application. MRI acquisition included T1- (precontrast and postcontrast) and T2-weighted sequences. SUV(mean), T1 contrast enhancement, and T2 signal intensity from region-of-interest analysis were calculated for different fascial and muscular compartments. In addition, musculoskeletal MRI findings and the modified Rodnan skin score were assessed. All patients underwent imaging follow-up. RESULTS: At baseline PET/MRI, ScGVHD-related musculoskeletal abnormalities consisted of increased signal and/or thickening of involved anatomical structures on T2-weighted and T1 postcontrast images as well as an increased FDG uptake. At follow-up, ScGVHD-related imaging findings decreased (SUV(mean) n = 4, mean T1 contrast enhancement n = 5, mean T2 signal intensity n = 3) or progressed (SUV(mean) n = 3, mean T1 contrast enhancement n = 2, mean T2 signal intensity n = 4). Clinically modified Rodnan skin score improved for 5 follow-ups and progressed for 2. SUV(mean) values correlated between PET/CT and PET/MRI acquisition (r = 0.660, P = 0.014), T1 contrast enhancement, and T2 signal (r = 0.668, P = 0.012), but not between the SUV(mean) values and the MRI parameters. CONCLUSIONS: PET/MRI as a combined morphological and functional technique seems to assess the inflammatory processes from different points of view and provides therefore in part complementary information.

Simultaneous 68Ga-DOTATOC-PET/MRI for IMRT treatment planning for meningioma: first experience.

PURPOSE: To evaluate intensity-modulated radiotherapy (IMRT) treatment planning based on simultaneous positron-emission tomography and magnetic resonance imaging (PET/MRI) of meningioma. METHODS AND MATERIALS: A meningioma patient was examined prior to radiotherapy with dedicated planning computed tomography (CT), MRI, PET/CT with gallium-68-labeled DOTATOC (68Ga-DOTATOC), and simultaneous 68Ga-DOTATOC-PET/MRI. The first gross target volume (GTV) was defined based on a combination of separate MR and 68Ga-DOTATOC-PET/CT imaging (GTVPET/CT+MR). Then, the simultaneous PET/MR images were used to delineate a second GTV (GTVPET/MR) by following exactly the same delineation strategy. After an isotropic expansion of those volumes by a 4-mm safety margin, the resulting planning target volumes (PTVs) were compared by calculating the intersection volume and the relative complements. A cross-evaluation of IMRT plans was performed, where the treatment plan created for the PTVPET/CT+MR was applied to the PET/MR-based PTVPET/MR. RESULTS: Generally, target volumes for IMRT treatment planning did not differ between MRI plus 68Ga-DOTATOC-PET/CT and simultaneous PET/MR imaging. Only in certain regions of the GTV were differences observed. The overall volume of the PET/MR-based PTV was approximately the same as that obtained from PET/CT data. A small region of infiltrative tumor growth next to the main tumor mass was better visualized with combined PET/MR due to smaller PET voxel sizes and improved recovery. An IMRT treatment plan was optimized for the PTVPET/CT+MR. The evaluation of this plan with respect to the PTVPET/MR showed parts of the target volume that would not have received the full radiation dose after delineation of the tumor, based on simultaneous PET/MR. CONCLUSION: This case showed that differences in target volumes delineated on the basis of separate MR and PET/CT and simultaneous PET/MR may be observed that can have significant consequences for an effectively applied radiotherapy treatment plan.