Automated lung cancer assessment on 18F-PET/CT using Retina U-Net and anatomical region segmentation.

OBJECTIVES: To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PET/CT. METHODS: A data set consisting of 364 FDG-PET/CTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PET/CT series. The data set was split into a training (n = 216), validation (n = 74), and internal test data set (n = 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FP/c) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PET/CTs from another institution. RESULTS: Sensitivity for T lesions was 86.2% (95% CI: 77.2-92.7) at a FP/c of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate = 88.8% (95% CI: 82.5-93.5%) and FP/c = 2.7). CONCLUSIONS: Retina U-Nets are a valuable tool for tumor detection tasks on PET/CT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available. KEY POINTS: • Detection of malignant lesions in PET/CT with Retina U-Net is feasible. • All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. • Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging.

Golden-Angle Radial Sparse Parallel (GRASP) MRI differentiates head & neck paragangliomas from schwannomas.

PURPOSE: The aim of this study was to demonstrate the value of DCE MRI with high spatiotemporal resolution (GRASP) for differentiating paragangliomas and schwannomas in the head and neck. METHODS: In a retrospective PACS search of in total 410 patients who had undergone head & neck GRASP-MRI, we identified 6 patients with biopsy proven cervical paragangliomas (n = 3) and schwannomas (n = 3). Conventional MRI features were evaluated, lesion size was determined. Postprocessing in 4D-GRASP datasets was performed (1) based on reconstructions with a temporal resolution (Tres) of 4.1 s, qualitative time-intensity curve classification and semiquantitative parameter (Tpeak, PH, ERmax and Slopemax) analysis, and (2) voxel-based mapping and qualitative and semiquantitative perfusion modeling based on reconstructions with a Tres of 1.6 s. Additionally, GRASP perfusion analysis was performed in another set of 5 patients with presumed cervical paragangliomas (n = 3) and schwannomas (n = 2) based on conventional imaging criteria and was correlated with conventional imaging findings. Due to the small sample size, both groups were compared qualitatively. RESULTS: In the time intensity curve classification of 4D GRASP reconstructions (Tres 4.1 s), biopsy proven paragangliomas were consistently characterized by a type-III rapid inflow wash-out pattern, compared to a type-I inflow pattern in the schwannoma group. In both temporal resolutions, semiquantitative analysis of time intensity curves demonstrated rapid wash-in, wash-out, and higher peak signal intensities in paragangliomas compared to schwannomas. In 5 presumed (non-biopsy-proven) paragangliomas and schwannomas, time intensity curves improved diagnostic certainty. CONCLUSIONS: Visual time intensity curve classification and semi-quantitative analysis of GRASP-MRI were, in this small retrospective series, sufficient to differentiate cervical paragangliomas from schwannomas. Utilization of this technique may further improve diagnostic confidence in lesions lacking conventional imaging features.

Correction to: Perfusion MRI in CNS disease: current concepts.

The above article was published with one author name being incorrect. The published paper states "H. von Tengg", whereas it should be "H. von Tengg-Kobligk". The author name has been corrected above.

Multimodal ultrasound tomography for breast imaging: a prospective study of clinical feasibility.

BACKGROUND: To describe the clinical set-up and evaluate the feasibility of multimodal ultrasound tomography (MUT) for breast imaging. METHODS: Thirty-two consecutive patients referred for breast imaging and 24 healthy volunteers underwent MUT. In the 32 patients, the examination discomfort was compared to that of mammography (n = 31), handheld ultrasound (HUS) (n = 27) and magnetic resonance imaging (MRI) (n = 4) on a scale from 1 (lowest discomfort) to 10 (highest discomfort). MUT investigation time was recorded. Findings automatically detected by MUT were correlated with conventional imaging and biopsy results. RESULTS: Breast MUT was well tolerated by all 56 participants; 55 bilateral exams were uneventful. During one exam, the digitalisation card failed and the exam was successfully repeated within three days. Mean examination discomfort was 1.6 (range = 1-5) for MUT, 1.5 (range = 1-5) for HUS, 5.3 (range = 3-7) for MRI, and 6.3 (range = 1-10) for mammography. MUT examination time was 38 ± 6 min (mean ± standard deviation). In the patients referred for breast imaging, MUT detected four lesions and indicated malignancy in three of these cases. These findings were confirmed by additional imaging and biopsy. CONCLUSION: MUT is feasible in a clinical context considering examination time and patient acceptance. These interesting initial diagnostic findings warrant further studies.

Volumetric alterations in the heteromodal association cortex in children with autism spectrum disorder.

BACKGROUND: We investigated if alterations in higher-order association areas related to schizophrenia, namely the heteromodal association cortex (HASC), are also observable in subjects with autism spectrum disorder (ASD). METHODS: A group of 18 children with ASD and 18 healthy controls (HC) underwent magnetic resonance imaging (MRI). The examination comprised an analysis of group differences in gray matter (GM) volume, surface area (SA) and hemispheric lateralization. RESULTS: Differences in GM volumes in children with ASD and HC were detected in frontal and parietal areas related to the HASC. No HASC structure that showed changes in GM volume exhibited differences in SA. Alterations in hemispheric lateralization between ASD and HC are seen in a frontal area of the HASC. CONCLUSIONS: Our results indicate that changes in HASC areas are not restricted to schizophrenia, but extend to other psychiatric disorders, namely ASD. The lacking group differences in SA indicate that changes in GM volume are possibly evoked by other variables than SA in children with ASD.

Interventional real-time ultrasound imaging with an integrated electromagnetic field generator.

PURPOSE: Ultrasound (US) guided procedures are frequently performed for diagnosis and treatment of many diseases. However, there are safety and procedure duration limitations in US-guided interventions due to poor image quality and inadequate visibility of medical instruments in the field of view. To address this issue, we propose an interventional imaging system based on a mobile electromagnetic (EM) field generator (FG) attached to a US probe. METHODS: A standard US probe was integrated with an EM FG to allow combined movement of the FG with real-time imaging to achieve (1) increased tracking accuracy for medical instruments are located near the center of the tracking volume, (2) increased robustness because the FG is distant to large metallic objects, and (3) reduced setup complexity since time-consuming placement of the FG is not required. The new integrated US-FG imaging system was evaluated by assessing tracking and calibration accuracy in a clinical setting. To demonstrate clinical applicability, the prototype US-EMFG probe was tested in needle puncture procedures. RESULTS: The mobile EMFG attached to a US probe yielded sub-millimeter tracking accuracy despite the presence of metal close to the FG. Calibration errors were in the range of 1-2 mm. In an initial phantom study on US-guided needle punctures, targeting errors of about 3 mm were achieved. CONCLUSION: A combined US-EMFG probe is feasible and effective for tracking medical instruments relative to US images with high accuracy and robustness while keeping hardware complexity low.

Whole-body-MR-diffusion weighted imaging in oncology.

UNLABELLED: The clinical implementation of whole body diffusion weighted imaging (WB-DWI) for tumor-detection, -characterization and therapy monitoring is well underway. The method is fast, robust and combined with its wide availability on modern MRI scanners, it has a vast potential clinical impact. Owing to the high tumor to background contrast, its main application areas are simple detection of tumor suspicious lesions (primary tumor, recurrence, and metastasis), tumor grading and therapy monitoring. WB-DWI has a strong diagnostic potential regarding the evaluation of bone marrow and its diseases and as thus, tumor detection and therapy monitoring of bone metastasis is of particular interest. The assessment of a lymphatic tumor spreading is constricted. One of the major hurdles that still hamper the wide clinical application of WB-DWI is a lack of standardization of measurement parameters that limit the comparability of current research results. KEY POINTS: ▶ Owing to the high tumor to background contrast WB-DWI allows fast assessment of tumor distribution and total tumor burden. ▶ WB-DWI allows therapy monitoring. ▶ WB-DWI is widely available.

Diffusion-weighted imaging in rectal carcinoma patients without and after chemoradiotherapy: a comparative study with histology.

Diffusion-weighted imaging (DWI) can be used to quantitatively assess functional parameters in rectal carcinoma that are relevant for prognosis and treatment response assessment. However, there is no consensus on the histopathological background underlying the findings derived from DWI. The aim of this study was to perform a comparison of DWI and histologic parameters in two groups of rectal carcinoma patients without (n=12) and after (n=9) neoadjuvant chemoradiotherapy (CRT). The intravoxel incoherent motion (IVIM) model was used to calculate the diffusion coefficient D and the perfusion fraction f in rectal carcinoma, the adjacent rectum and fat in the two patient groups. Immunohistological analysis was performed to assess the cellularity, vascular area fraction and vessel diameter for comparison and correlation. Out of 36 correlations between parameters from DWI and histology, four were found to be significant. In rectal carcinoma of patients without CRT, the diffusion D and the perfusion f correlated with the vascular area fraction, respectively, which could not be found in the group of patients who received CRT. Further correlations were found for the rectum and fat. Histological evaluation revealed significant differences between the tissues on the microscopic level concerning the cellular and vascular environment that influence diffusion and perfusion. In conclusion, DWI produces valuable biomarkers for diffusion and perfusion in rectal carcinoma and adjacent tissues that are highly dependent of the underlying cellular microenvironment influenced by structural and functional changes as well as the administered treatment, and consequently can be beyond histological ascertainability.

Whole-body-MR-diffusion weighted imaging in oncology.

UNLABELLED: The clinical implementation of whole body diffusion weighted imaging (WB-DWI) for tumor-detection, -characterization and therapy monitoring is well underway. The method is fast, robust and combined with its wide availability on modern MRI scanners, it has a vast potential clinical impact. Owing to the high tumor to background contrast, its main application areas are simple detection of tumor suspicious lesions (primary tumor, recurrence, and metastasis), tumor grading and therapy monitoring.WB-DWI has a strong diagnostic potential regarding the evaluation of bone marrow and its diseases and as thus, tumor detection and therapy monitoring of bone metastasis is of particular interest. The assessment of a lymphatic tumor spreading is constricted. One of the major hurdles that still hamper the wide clinical application of WB-DWI is a lack of standardization of measurement parameters that limit the comparability. of current research results. KEY POINTS: Owing to the high tumor to background contrast WB-DWI allows fast assessment of tumor distribution and total tumor burden. WB-DWI allows therapy monitoring. WB-DWI is widely available.

MITK diffusion imaging.

BACKGROUND: Diffusion-MRI provides a unique window on brain anatomy and insights into aspects of tissue structure in living humans that could not be studied previously. There is a major effort in this rapidly evolving field of research to develop the algorithmic tools necessary to cope with the complexity of the datasets. OBJECTIVES: This work illustrates our strategy that encompasses the development of a modularized and open software tool for data processing, visualization and interactive exploration in diffusion imaging research and aims at reinforcing sustainable evaluation and progress in the field. METHODS: In this paper, the usability and capabilities of a new application and toolkit component of the Medical Imaging and Interaction Toolkit (MITK, www.mitk.org), MITK-DI, are demonstrated using in-vivo datasets. RESULTS: MITK-DI provides a comprehensive software framework for high-performance data processing, analysis and interactive data exploration, which is designed in a modular, extensible fashion (using CTK) and in adherence to widely accepted coding standards (e.g. ITK, VTK). MITK-DI is available both as an open source software development toolkit and as a ready-to-use installable application. CONCLUSIONS: The open source release of the modular MITK-DI tools will increase verifiability and comparability within the research community and will also be an important step towards bringing many of the current techniques towards clinical application.

IVIM-DWI of transplanted kidneys: reduced diffusion and perfusion dependent on cold ischemia time.

PURPOSE: To evaluate the effect of cold ischemia time (CIT) of renal allografts on diffusion and perfusion using intravoxel incoherent motion (IVIM) derived parameters. MATERIAL AND METHODS: A total of 37 patients with renal allografts (CIT: 27 <15 h, 10 ≥15 h) and 30 individuals with healthy kidneys were examined at 1.5 T using a single-shot echo-planar diffusion-weighted pulse sequence with nine b-values ranging from 0 to 800 s/mm(2). ADC, perfusion fraction f, and the diffusion coefficient D were calculated using the IVIM model. Parameters of allografts stratified by CIT were compared with healthy kidney groups using the Mann-Whitney U test for unpaired data. We computed the Spearman correlation coefficient for correlation with creatinine values. RESULTS: ADC, D, and f of transplanted kidneys were significantly lower than in the healthy controls. The long-CIT group showed significantly lower diffusion parameters compared with the short-CIT group [mean±SD]: ADC: 1.63±0.14 µm(2)/ms, f: 11.90±5.22%, D: 1.55±0.25 µm(2)/ms versus ADC: 1.79±0.13 µm(2)/ms, f: 16.12±3.43%, D: 1.73±0.14 µm(2)/ms, P(ADC), (f), (D)<0.05. CONCLUSION: Our results suggest that diffusion parameters, especially the ADC, depend on the CIT of the kidney allograft. Potentially, this stands for functional changes in renal allografts. Diffusion-weighted imaging could be used for follow-up examinations. Thus, diffusion parameters may help guide therapy in patients with delayed graft function.

Investigation of renal lesions by diffusion-weighted magnetic resonance imaging applying intravoxel incoherent motion-derived parameters--initial experience.

PURPOSE: Usefulness of biexponentially fitted signal attenuation at different b-values for differentiating the histological characteristics of renal tumors. MATERIALS AND METHODS: A total of 26 patients with 28 renal masses (histologically proven: 20 clear cell renal cell carcinomas [ccRCC], three transitional cell carcinomas, two oncocytomas, and one papillary RCC) and 30 volunteers with healthy kidneys were examined at 1.5 Tesla using an echo-planar DWI sequence. Using the IVIM model, we calculated the perfusion fraction f and the diffusion coefficient D. Furthermore, the ADC was obtained. These tumor parameters were compared to healthy renal tissue nonparametrically, and a receiver operating characteristic (ROC) analysis was performed. RESULTS: Healthy renal parenchyma showed higher ADC and D values (p<0.001) than ccRCC (ADC 1.95±0.10 [SD] µm2/ms, f 18.32±2.52%, and D 1.88±0.11 µm2/ms versus ADC 1.45±0.38 µm2/ms, f 18.59±6.16%, and D 1.34±0.38 µm2/ms). When detecting malignancies the area under the curve for D was higher than for ADC. The f values for ccRCC were higher (p<0.001) than for non-ccRCC (ADC 1.52±0.47 µm2/ms, f 8.44±1.24%, and D 1.30±0.18 µm2/ms). Both f and D correlated with ccRCC grading. CONCLUSION: IVIM imaging is able to provide reliable diffusion values in the human kidney and may enhance the accuracy of tumor diagnosis. The D value was the best parameter to distinguish renal tumors from healthy renal tissue. The f value is promising for determining the histological subgroups.

[Mild cognitive impairment: diagnostic value of different MR techniques]. / "Mild cognitive impairment": Diagnostische Wertigkeit verschiedener MR-Techniken.

In view of an increasingly aging population the prevalence of dementia is also expected to increase rapidly. As well as clinical, neuropsychological and laboratory procedures magnetic resonance imaging (MRI) plays an important role in the early diagnosis of dementia which is important in the precursor stage of mild cognitive impairment (MCI). On the one hand this stage is associated with an increased risk of dementia and on the other hand an early treatment in this stage could attenuate development of the disease. In addition to morphological changes different functional MRI techniques can help in the early diagnosis of dementia and the precursor stages. Moreover, it is important to detect those MCI patients who are at particularly risk for developing dementia. In the differentiation of converters to non-converters initial studies suggest that particularly voxel-based morphometry, MR spectroscopy and diffusion tensor imaging can provide important additional information.

[Introduction to the basic principles and techniques of diffusion-weighted imaging]. / Einführung in die Grundlagen und Techniken der Diffusionsbildgebung.

This article gives an overview of the many different technical aspects of diffusion-weighted imaging and a review of the physical and mathematical background. Specific terms, such as free and restricted diffusion are introduced and elucidated. The measurement of diffusion by magnetic resonance imaging (MRI) and which phenomena can occur are described. Finally, an overview of current developments in diffusion imaging and its application in research is presented.

[Treatment options for arteriovenous malformations]. / Therapieoptionen bei arteriovenösen Malformationen.

Cerebral arteriovenous malformations are errors in the development of vasculature with shunts between cerebral arteries and veins, which manifest predominantly as intracerebral hemorrhage. To prevent hemorrhage, a complete obliteration of the arteriovenous malformation is necessary. For this purpose, techniques of microsurgery, radiotherapy, and embolization alone or in combination are available. This review article presents the treatment options and also summarizes available data from the literature on which therapy should be chosen in which situation and when watchful waiting should be preferred.

[Functional imaging for brain tumors (perfusion, DTI and MR spectroscopy)]. / Funktionelle Bildgebung bei Hirntumoren (Perfusion, DTI, MR-spektroskopie).

This contribution considers the possibilities involved with using functional methods in magnetic resonance imaging (MRI) diagnostics for brain tumors. Of the functional methods available, we discuss perfusion MRI (PWI), diffusion MRI (DWI and DTI) and MR spectroscopy (H-MRS). In cases of brain tumor, PWI aids in grading and better differentiation in diagnostics as well as for pre-therapeutic planning. In addition, the course of treatment, both after chemo- as well as radiotherapy in combination with surgical treatment, can be optimized. PWI allows better estimates of biological activity and aggressiveness in low grade brain tumors, and in the case of WHO grade II astrocytoma showing anaplasically transformed tumor areas, allows more rapid visu-alization and a better prediction of the course of the disease than conventional MRI diagnostics. Diffusion MRI, due to the directional dependence of the diffusion, can illustrate the course and direction of the nerve fibers, as well as reconstructing the nerve tracts in the cerebrum, pons and cerebellum 3-dimensionally. Diffusion imaging can be used for describing brain tumors, for evaluating contralateral involvement and the course of the nerve fibers near the tumor. Due to its operator dependence, DTI based fiber tracking for defining risk structures is controversial. DWI can also not differentiate accurately between cystic and necrotic brain tumors, or between metastases and brain abscesses. H-MRS provides information on cell membrane metabolism, neuronal integrity and the function of neuronal structures, energy metabolism and the formation of tumors and brain tissue necroses. Diagnostic problems such as the differentiation between neoplastic and non-neoplastic lesions, grading cerebral glioma and distinguishing between primary brain tumors and metastases can be resolved. An additional contribution will discuss the control of the course of glial tumors after radiotherapy.

Diffusion tensor imaging-based fractional anisotropy quantification in the corticospinal tract of patients with amyotrophic lateral sclerosis using a probabilistic mixture model.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), fiber degeneration within the corticospinal tract (CST) can be quantified by diffusion tensor imaging (DTI) as an indirect marker of upper motor neuron involvement. A new method of measuring quantitative DTI parameters using a probabilistic mixture model for fiber tissue and background in the corticospinal tract of patients with ALS is evaluated. MATERIALS AND METHODS: Axial echo-planar imaging (EPI) DTI datasets (6 gradient directions, 10 repetitions) were acquired for 10 patients and 20 healthy control subjects. The diffusion tensor was visualized in a multiplanar viewer using a unique color coding method. Pure fiber tissue inside a region is separated from background and mixture voxels using a probabilistic mixture model. This allows for a reduction of errors as a result of partial volume effects and measurement variability. RESULTS: Fractional anisotropy (FA) was measured within the CST at levels ranging from internal capsule to pons. Mean coefficients of variation of intrarater, scan-rescan, and inter-rater reproducibility were 2.4%, 3.0%, and 5.7%, respectively. Optimal measurement positions along the CST with respect to minimum variability and maximum difference between patients and healthy subjects were identified in the caudal half of the internal capsule. Moreover, a negative correlation between the age-corrected FA and the disease duration but not the ALS Severity scale score was found. CONCLUSION: The new software for fiber integrity quantification is suited to assess FA in the corticospinal tract with high reproducibility. Thus, this tool can be useful in future studies for monitoring disease status and potential treatment efficiency.

Detection of tumour infiltration in axonal fibre bundles using diffusion tensor imaging.

We present a method for the detection and quantification of white matter infiltration from human brain tumours based on Diffusion Tensor Imaging (DTI). Since white matter destruction alters the local diffusion properties, DTI has the potential to sensitively detect tumour infiltration and to quantify the degree thereof. Here, we consider three tumour patients with gliomas, two with and one without contralateral tumour progress. We use DTI to identify specific fibre systems, where infiltration has to be assessed. On this basis, the problem of arbitrary region of interest definition is solved such that tumour infiltration can be reliably quantified in particular fibre bundles. It is demonstrated at the Corpus Callosum (CC) and the Pyramidal Tract (PT) that fibre bundle infiltration can be well detected by specific visualisation techniques of diffusion tensor data. Infiltration of the CC is quantified by using a reliable method for the determination of diffusion properties inside particular fibre bundles. For an age normalised quantification of white matter infiltration we introduce the Integrity Index, which measures the diffusion anisotropy inside an infiltrated fibre bundle normalised by the diffusion anisotropy in a specific region of healthy fibre tissue. It turns out that the quantification of CC infiltration correlates with contralateral tumour progression and has the potential to serve as a surrogate marker for this process, which is crucial for surgical therapy decisions and intervention planning.

Perfusion MRI in CNS disease: current concepts.

Today there are several indications for cerebral perfusion MRI. The major indications routinely used in increasing numbers of imaging centers include cerebrovascular disease, tumor imaging and recently psychiatric disorders. Perfusion MRI is based on the injection of a gadolinium chelate and the rapid acquisition of images as the bolus of contrast agent passes through the blood vessels in the brain. The contrast agent causes a signal change; this signal change over time can be analysed to measure cerebral hemodynamics. The quality of brain perfusion studies is very dependent on the contrast agent used: a robust and strong signal decrease with a compact bolus is needed. MultiHance (gadobenate dimeglumine, Gd-BOPTA) is the first of a new class of paramagnetic MR contrast agents with a weak affinity for serum proteins. Due to the interaction of Gd-BOPTA with serum albumin, MultiHance presents with significantly higher T1- and T2-relaxivities enabling a sharper bolus profile. This article reviews the indications of perfusion MRI and the performance of MultiHance in MR perfusion of different diseases. Previous studies using perfusion MRI for a variety of purposes required the use of double dose of contrast agent to achieve a sufficiently large signal drop to enable the acquisition of a clear input function and the calculation of perfusion rCBV and rCBF maps of adequate quality. Recent studies with Multi-Hance suggest that only a single dose of this agent is needed to cause a signal drop of about 30% which is sufficient to allow the calculation of high quality rCBV and rCBF maps.