Suitability of DNN-based vessel segmentation for SIRT planning.

PURPOSE: The segmentation of the hepatic arteries (HA) is essential for state-of-the-art pre-interventional planning of selective internal radiation therapy (SIRT), a treatment option for malignant tumors in the liver. In SIRT a catheter is placed through the aorta into the tumor-feeding hepatic arteries, injecting small beads filled with radiation emitting material for local radioembolization. In this study, we evaluate the suitability of a deep neural network (DNN) based vessel segmentation for SIRT planning. METHODS: We applied our DNN-based HA segmentation on 36 contrast-enhanced computed tomography (CT) scans from the arterial contrast agent phase and rated its segmentation quality as well as the overall image quality. Additionally, we applied a traditional machine learning algorithm for HA segmentation as comparison to our deep learning (DL) approach. Moreover, we assessed by expert ratings whether the produced HA segmentations can be used for SIRT planning. RESULTS: The DL approach outperformed the traditional machine learning algorithm. The DL segmentation can be used for SIRT planning in [Formula: see text] of the cases, while the reference segmentations, which were manually created by experienced radiographers, are sufficient in [Formula: see text]. Seven DL cases cannot be used for SIRT planning while the corresponding reference segmentations are sufficient. However, there are two DL segmentations usable for SIRT, where the reference segmentations for the same cases were rated as insufficient. CONCLUSIONS: HA segmentation is a difficult and time-consuming task. DL-based methods have the potential to support and accelerate the pre-interventional planning of SIRT therapy.

Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany.

The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals' quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure.

Improving automatic liver tumor segmentation in late-phase MRI using multi-model training and 3D convolutional neural networks.

Automatic liver tumor segmentation can facilitate the planning of liver interventions. For diagnosis of hepatocellular carcinoma, dynamic contrast-enhanced MRI (DCE-MRI) can yield a higher sensitivity than contrast-enhanced CT. However, most studies on automatic liver lesion segmentation have focused on CT. In this study, we present a deep learning-based approach for liver tumor segmentation in the late hepatocellular phase of DCE-MRI, using an anisotropic 3D U-Net architecture and a multi-model training strategy. The 3D architecture improves the segmentation performance compared to a previous study using a 2D U-Net (mean Dice 0.70 vs. 0.65). A further significant improvement is achieved by a multi-model training approach (0.74), which is close to the inter-rater agreement (0.78). A qualitative expert rating of the automatically generated contours confirms the benefit of the multi-model training strategy, with 66 % of contours rated as good or very good, compared to only 43 % when performing a single training. The lesion detection performance with a mean F1-score of 0.59 is inferior to human raters (0.76). Overall, this study shows that correctly detected liver lesions in late-phase DCE-MRI data can be automatically segmented with high accuracy, but the detection, in particular of smaller lesions, can still be improved.

Antibody-Negative Paraneoplastic Autoimmune Multiorgan Syndrome (PAMS) in a Patient with Follicular Lymphoma Accompanied by an Excess of Peripheral Blood CD8+ Lymphocytes.

Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune disease associated with malignancies. Here, we present a patient initially misdiagnosed with "chronic" Stevens-Johnson syndrome. Over a year later, the patient was diagnosed with stage IV follicular lymphoma and treated with an anti-CD20 antibody. At this time, his skin condition had significantly worsened, with erythroderma and massive mucosal involvement, including in the mouth, nose, eyes, and genital region. Histopathology revealed lichenoid infiltrates with interface dermatitis, dyskeratoses, necrotic keratinocytes, and a dense CD8+ infiltrate with strong epidermotropism. Direct and indirect immunofluorescence tests for autoantibodies were negative. Remarkably, we retrospectively discovered a chronic increase in peripheral CD8+ lymphocytes, persisting for over a year. Consequently, the patient was diagnosed with antibody-negative PAMS. Three weeks later, he succumbed to respiratory failure. This dramatic case highlights the challenges in diagnosing PAMS, particularly in cases where immunofluorescence assays are negative. Importantly, we observed, for the first time, a chronic excess of CD8+ peripheral blood lymphocytes, associated with PAMS, consistent with the systemic, autoreactive T-cell-driven processes that characterize this condition.

Unilateral Choanal Atresia: Indications of Long-Term Olfactory Deficits and Volumetric Brain Changes Postsurgically.

BACKGROUND: Very few studies have investigated whether unilateral choanal atresia is associated with permanent olfactory deficits. OBJECTIVE: This study aimed to evaluate the olfactory performance of patients with unilateral choanal atresia postsurgically. METHODS: Three patients with unilateral atresia were examined in terms of olfactory performance with the Sniffin' Sticks test (odor identification, threshold, and discrimination), size of the olfactory bulb, and volumetric brain changes. RESULTS: All patients demonstrated significantly lower olfactory performance in terms of odor threshold on the same side with the choanal atresia. Grey matter reductions were found ipsilaterally in the hippocampus. CONCLUSIONS: This pilot study indicates that persistent olfactory deficits and volumetric brain changes are present in patients with unilateral choanal atresia.

Improved Odor Identification Ability and Increased Regional Gray Matter Volume After Olfactory Training in Patients With Idiopathic Olfactory Loss.

Idiopathic olfactory loss (IOL) is thought as an early marker for neurodegenerative disease. This study investigated the effect of olfactory training (OT) on regional gray matter volume (GMV) among patients with IOL. A total of 24 patients (mean age 64.6 years, 11 male) with IOL and 30 control participants with normal olfaction (mean age 62.6 years, 13 males) were included in the study. Voxel-based morphometry was performed to compare the GMV between patient and control groups. Only the patients received OT (averaged duration 7 months), and a longitudinal approach was used to examine the GMV change from pre- to post-OT. Moreover, the effect of OT on GMV change was explored for patients with different severity of olfactory loss (anosmia vs. hyposmia). Olfactory performance was measured alongside using the "Sniffin' Sticks." Patients had improved odor identification and larger GMV in the bilateral cerebellum, bilateral thalamus, left precentral gyrus, right gyrus rectus, and medial orbitofrontal cortex after OT. However, no correlation was found between changes of odor identification and increased regional GMV. Besides, patients with anosmia, compared with patient with hyposmia, demonstrated increased GMV in the left precuneus, left superior frontal medial cortex, and left midcingulate cortex after OT. The study showed improved odor identification ability among patients with IOL after OT, which is unlikely related to spontaneous recovery. In this specific patient group, the GMV alterations may be associated with factors not directly predicted by the currently performed measurements, but possibly higher order olfactory-related functional changes.

Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a non-randomized, monocentric phase II clinical trial-PaCa-DD-041 (Eudra-CT 2009-011968-11).

BACKGROUND: Pancreatic cancer is a devastating disease with a 5-year survival rate of 20-25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy. METHODS: Patients with histologically proven resectable, borderline resectable or unresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the standardized uptake value (SUV) measured with FDG-PET. Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was performed using contrast-enhanced CT and contrast-enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen. RESULTS: A total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal SUV (SUVmax) during therapy (p < 0.001). Using the mean apparent diffusion coefficient (ADC), response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7-38 months). CONCLUSION: Based on these limited patient numbers, it was possible to show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. FDG-PET/CT may be a reliable method to evaluate response to the combined therapy. In contrast, when evaluating the response using mean ADC, DW-MRI did not show conclusive results.

Prognosis in patients with synchronous colorectal cancer metastases after complete resection of the primary tumor and the metastases.

BACKGROUND: Synchronous metastases are considered a negative prognostic factor in patients with metastatic colorectal cancer (CRC). We investigated the outcomes of stage IV CRC patients undergoing complete gross resection (R0/1) of both the primary tumor and the metastases under the guidance of a multidisciplinary team (MDT). METHODS: All CRC patients with synchronous metastases were retrieved from a prospective database. Patients treated from 2006 to 2017 who underwent complete resection were analyzed. Various factors, including multiple metastatic sites and complex procedures, were investigated. Univariate and multivariate overall survival (OS) calculations were performed. RESULTS: Of 330 consecutive patients with synchronous metastases, 101 (30.6%) achieved an R0/1 status including 12 (11.9%) patients with multiple metastatic sites. Complex procedures were necessary in 45 (44.6%) patients. Five-year OS was 53.0% for the R0/1 patient group. Multivariate analysis could not detect factors associated with prognosis. CONCLUSIONS: With modern treatment, the prognosis of patients with synchronous CRC metastases can be improved. Decisions made by a MDT offered one-third of patients a potentially curative approach to their stage IV disease. Despite the treatment of a high rate of patients with complex metastases necessitating complex procedures, we achieved a favorable 5-year OS rate.

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis-an animal experimental prospective cohort study.

BACKGROUND: This study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads). RESULTS: In both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p < 0.001], higher microvessel density (MVD) determined histologically after CD-31 staining [171.4 (± 18.9) as compared to 110.8 (± 11) vessels per mm2, p = 0.002], and higher perfusion as indicated by the number of beads [1.3 (± 0.1) as compared to 1.1 (± 0.04) beads per field of view, p = 0.001]. In [18F]FDG-PET/CT, co-transplanted tumors revealed significantly higher standardized uptake values [SUVmax, 2.8 (± 0.2) as compared to 1.1 (± 0.1), p < 0.001] and larger metabolic active volumes [2.4 (± 0.2) as compared to 0.4 (± 0.2) cm3, p < 0.001] than non-co-transplanted tumors. There were significant correlations for vascularization parameters derived from histology and [18F]FDG PET/CT [beads and SUVmax, r = 0.353, p = 0.005; CD-31 and SUVmax, r = 0.294, p = 0.036] as well as between CE-CT and [18F]FDG PET/CT [contrast enhancement and SUVmax, r = 0.63, p < 0.001; vital CT tumor volume and metabolic PET tumor volume, r = 0.919, p < 0.001]. CONCLUSIONS: In this study, a human xenograft tumor model with modifiable vascularization implementable for imaging, pharmacological, and radiation therapy studies was successfully established. Both [18F]FDG-PET/CT and CE-CT are capable to detect parameters closely connected to the degree of tumor vascularization, thus they can help to evaluate vascularization in tumors noninvasively. [18F]FDG-PET may be considered for characterization of tumors beyond pure glucose metabolism and have much greater contribution to diagnostics in oncology.

Reducing inter-observer variability and interaction time of MR liver volumetry by combining automatic CNN-based liver segmentation and manual corrections.

PURPOSE: To compare manual corrections of liver masks produced by a fully automatic segmentation method based on convolutional neural networks (CNN) with manual routine segmentations in MR images in terms of inter-observer variability and interaction time. METHODS: For testing, patient's precise reference segmentations that fulfill the quality requirements for liver surgery were manually created. One radiologist and two radiology residents were asked to provide manual routine segmentations. We used our automatic segmentation method Liver-Net to produce liver masks for the test cases and asked a radiologist assistant and one further resident to correct the automatic results. All observers were asked to measure their interaction time. Both manual routine and corrected segmentations were compared with the reference annotations. RESULTS: The manual routine segmentations achieved a mean Dice index of 0.95 and a mean relative error (RVE) of 4.7%. The quality of liver masks produced by the Liver-Net was on average 0.95 Dice and 4.5% RVE. Liver masks resulting from manual corrections of automatically generated segmentations compared to routine results led to a significantly lower inter-observer variability (mean per case absolute RVE difference across observers 0.69%) when compared to manual routine ones (2.75%). The mean interaction time was 2 min for manual corrections and 10 min for manual routine segmentations. CONCLUSIONS: The quality of automatic liver segmentations is on par with those from manual routines. Using automatic liver masks in the clinical workflow could lead to a reduction of segmentation time and a more consistent liver volume estimation across different observers.

Multimodal image registration for liver radioembolization planning and patient assessment.

PURPOSE: Multimodal imaging plays a key role in patient assessment and treatment planning in liver radioembolization. It will reach its full potential for convenient use in combination with deformable image registration methods. A registration framework is proposed for multimodal liver image registration of multi-phase CT, contrast-enhanced late-phase T1, T2, and DWI MRI sequences. METHODS: A chain of four pair-wise image registrations based on a variational registration framework using normalized gradient fields as distance measure and curvature regularization is introduced. A total of 103 cases of 35 patients was evaluated based on anatomical landmarks and deformation characteristics. RESULTS: Good anatomical correspondence and physical plausibility of the deformation fields were attained. The global mean landmark errors vary from 3.20 to 5.36 mm, strongly influenced by low resolved images in z-direction. Moderate volume changes are indicated by mean minimum and maximum Jacobian determinants of 0.44 up to 1.88. No deformation foldings were detected. The mean average divergence of the deformation fields range from 0.08 to 0.16 and the mean harmonic energies vary from 0.08 to 0.58. CONCLUSION: The proposed registration solutions enable the combined use of information from multimodal imaging and provide an excellent basis for patient assessment and primary planning for liver radioembolization.

FMISO-PET-based lymph node hypoxia adds to the prognostic value of tumor only hypoxia in HNSCC patients.

PURPOSE: This secondary analysis of the prospective study on repeat [18F]fluoromisonidazole (FMISO)-PET in patients with locally advanced head and neck squamous cell carcinomas (HNSCC) assessed the prognostic value of synchronous hypoxia in primary tumor (Tu) and lymph node metastases (LN), and evaluated whether the combined reading was of higher prognostic value than that of primary tumor hypoxia only. METHODS: This analysis included forty-five LN-positive HNSCC patients. FMISO-PET/CTs were performed at baseline, weeks 1, 2 and 5 of radiochemotherapy. Based on a binary scale, Tu and LN were categorized as hypoxic or normoxic, and two prognostic parameters were defined: Tu-hypoxia (independent of the LN oxygenation status) and synchronous Tu-and-LN-hypoxia. In fifteen patients with large LN (N = 21), additional quantitative analyses of FMISO-PET/CTs were performed. Imaging parameters at different time-points were correlated to the endpoints, i.e., locoregional control (LRC), local control (LC), regional control (RC) and time to progression (TTP). Survival curves were estimated using the cumulative incidence function. Univariable and multivariable Cox regression was used to evaluate the prognostic impact of hypoxia on the endpoints. RESULTS: Synchronous Tu-and-LN-hypoxia was a strong adverse prognostic factor for LC, LRC and TTP at any of the four time-points (p ≤ 0.004), whereas Tu-hypoxia only was significantly associated with poor LC and LRC in weeks 2 and 5 (p ≤ 0.047), and with TTP in week 1 (p = 0.046). The multivariable analysis confirmed the prognostic value of synchronous Tu-and-LN-hypoxia regarding LRC (HR = 14.8, p = 0.017). The quantitative FMISO-PET/CT parameters correlated with qualitative hypoxia scale and RC (p < 0.001, p ≤ 0.033 at week 2, respectively). CONCLUSIONS: This secondary analysis suggests that combined reading of primary tumor and LN hypoxia adds to the prognostic information of FMSIO-PET in comparison to primary tumor assessment alone in particular prior and early during radiochemotherapy. Confirmation in ongoing trials is needed before using this marker for personalized radiation oncology.

Landmark-based evaluation of a deformable motion correction for DCE-MRI of the liver.

PURPOSE: Annotation of meaningful landmark ground truth on DCE-MRI is difficult and laborious. Motion correction methods applied to DCE-MRI of the liver are thus mostly evaluated using qualitative or indirect measures. We propose a novel landmark annotation scheme that facilitates the generation of landmark ground truth on larger clinical datasets. METHODS: In our annotation scheme, landmarks are equally distributed over all time points of all available dataset cases and annotated by multiple observers on a per-pair basis. The scheme is used to annotate 26 DCE-MRI of the liver. A subset of the ground truth is used to optimize parameters of a deformable motion correction. Several variants of the motion correction are evaluated on the remaining cases with respect to distances of corresponding landmarks after registration, deformation field properties, and qualitative measures. RESULTS: A landmark ground truth on 26 cases could be generated in under 12 h per observer with a mean inter-observer distance below the mean voxel diagonal. Furthermore, the landmarks are spatially well distributed within the liver. Parameter optimization significantly improves the performance of the motion correction, and landmark distance after registration is 2 mm. Qualitative evaluation of the motion correction reflects the quantitative results. CONCLUSIONS: The annotation scheme makes a landmark-based evaluation of motion corrections for hepatic DCE-MRI practically feasible for larger clinical datasets. The comparably large number of cases enables both optimization and evaluation of motion correction methods.

Explorative analysis of IPA-SPECT data through statistical inference for an automated diagnosis of glioma tumor.

PURPOSE: The identification of a brain tumor imaged with PET or SPECT is usually performed with visual inspection of an expert medical clinician. However an automated diagnostic of such images hasn't been established or applied. In this study, we explored the possibility of establishing an automated statistical analysis for the diagnosis of glioma by means of IPA-SPECT data. METHODS: On the basis of a dataset of 100 patients that have undergone MRI and IPA-SPECT acquisition, in this work, we identify an automated workflow. Three different approaches were explored: I. statistical non-parametric mapping analysis (SnPM), II. statistical non-parametric analysis with an increased number of permutations due to sign-flipping function (PALM) and III. statistical parametric analysis (SPM). The automated methods were compared with the visual inspection. RESULTS: The study proved PALM and SPM approaches to have a high diagnostic power. Compared to the parametric methods, the non-parametric method is the mathematically correct approach for the problem in question. If we take the high resolution structural MRI information into account, the diagnostic power of PALM was not significantly inferior to the visual inspection (P = 0.5150), showing an area under the ROC curve (AUC) smaller only by less than 3%. CONCLUSIONS: The automated diagnostic method based on statistical inference, here applied to diagnose glioma tumors in IPA-SPECT data, seems to be a promising tool that can support the visual investigation in nuclear medicine. Moreover in the foreseeable future, the presented methodology has a big potential in various application like localization of active tumor tissues in surgical resection or stereotactic radiosurgery.

Predictive SIRT dosimetry based on a territorial model.

BACKGROUND: In the planning of selective internal radiation therapy (SIRT) for liver cancer treatment, one major aspect is to determine the prescribed activity and to estimate the resulting absorbed dose inside normal liver and tumor tissue. An optimized partition model for SIRT dosimetry based on arterial liver territories is proposed. This model is dedicated to characterize the variability of dose within the whole liver. For an arbitrary partition, the generalized absorbed dose is derived from the classical partition model. This enables to consider normal liver partitions for each arterial perfusion supply area and one partition for each tumor for activity and dose calculation. The proposed method excludes a margin of 11 mm emitting range around tumor volumes from normal liver to investigate the impact on activity calculation. Activity and dose calculation was performed for five patients using the body-surface-area (BSA) method, the classical and territorial partition model. RESULTS: The territorial model reaches smaller normal liver doses and significant higher tumor doses compared to the classical partition model. The exclusion of a small region around tumors has a significant impact on mean liver dose. Determined tumor activities for the proposed method are higher in all patients when limited by normal liver dose. Activity calculation based on BSA achieves in all cases the lowest amount. CONCLUSIONS: The territorial model provides a more local and patient-individual dose distribution in normal liver taking into account arterial supply areas. This proposed arterial liver territory-based partition model may be used for SPECT-independent activity calculation and dose prediction under the condition of an artery-based simulation for particle distribution.

On the Reliability of Automatic Volume Delineation in Low-Contrast [(18)F]FMISO-PET Imaging.

Hypoxia is a marker of poor prognosis in malignant tumors independent from the selected therapeutic method and the therapy should be intensified in such tumors. Hypoxia imaging with positron emission tomography (PET) is limited by low contrast to noise ratios with every available tracer. In radiation oncology appropriate delineation is required to allow therapy and intensification. While manual segmentation results are highly dependent from experience and observers condition (high inter- and intra observer variability), threshold- and gradient-based algorithms for automatic segmentation frequently fail in low contrast data sets. Likewise, calibration of these algorithms using phantoms is not useful. Complex computational models such as swarm intelligence-based algorithms are promising tools for optimized segmentation results and allow observer independent interpretation of multimodal and multidimensional imaging data.

Spatial distribution of FMISO in head and neck squamous cell carcinomas during radio-chemotherapy and its correlation to pattern of failure.

BACKGROUND: Tumour hypoxia can be measured by FMISO-PET and negatively impacts local tumour control in patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy. The aim of this post hoc analysis of a prospective clinical trial was to investigate the spatial variability of FMISO hypoxic subvolumes during radio-chemotherapy and the co-localisation of these volumes with later recurrences as a basis for individualised dose prescription trials with dose escalation defined by FMISO-PET. METHODS: Sequential FMISO scans of 12 (of 25) patients presenting residual hypoxia taken before (FMISOpre) and during (FMISOw1-FMISOw5) radio-chemotherapy were analysed regarding the stability of the FMISO subvolumes and, in case of local failure, their correlation to local relapse. RESULTS: Consecutive FMISO-PET positive volumes could be classified as moderately stable with Dice conformity indices of 62% and 58% up to the second week of treatment. Substantial volumetric variation during treatment was observed, with more than 20% geographic miss in all patients and more than 40% in half of the patients. The localisation of the maximum standardised uptake value (SUVmax) differed with a mean distance of 7.0 mm and 13.5 mm between the pre-therapeutic and first or second FMISO-PET during treatment. A stable hypoxic consensual volume (i.e. overlap of pre-therapeutic FMISO and intra-treatment FMISO subvolumes up to week two, generated by different contouring methods) was determined for six patients with imaging information of local recurrence. Three of these six local recurrences were located within this consensual volume. CONCLUSIONS: Our data suggest that selective dose painting to hypoxic tumour subvolumes requires adaptation during treatment and sufficient margins. An alternative strategy is to escalate the dose to the gross tumour volume, accepting lesser escalation of dose outside hypoxic areas if indicated by constraints for organs at risk.

Impact of chemotherapy for childhood leukemia on brain morphology and function.

OBJECTIVE: Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. METHODS: We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15-22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB's integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. RESULTS: Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. INTERPRETATION: Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.

Effect of MRI acoustic noise on cerebral fludeoxyglucose uptake in simultaneous MR-PET imaging.

UNLABELLED: Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. METHODS: The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. RESULTS: Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P < 0.05 (corrected) was used; however, a P < 0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]). CONCLUSIONS: Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude.

Prostate-specific antigen-negative prostate cancer recurrence?

We describe a patient with bone metastases occurring shortly after radical prostatectomy for organ-confined prostate cancer. The medical history and immunohistochemical findings suggested prostate cancer recurrence to the skeleton. Undetectable serum prostate-specific antigen levels, however, raised doubts about this diagnosis. A whole body (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scan was obtained and revealed a right-sided breast cancer as the primary site of metastatic spread.