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PURPOSE: To develop and validate a data acquisition scheme combined with a motion-resolved reconstruction and dictionary-matching-based parameter estimation to enable free-breathing isotropic resolution self-navigated whole-liver simultaneous water-specific T 1 $$ {\mathrm{T}}_1 $$ ( wT 1 $$ {\mathrm{wT}}_1 $$ ) and T 2 $$ {\mathrm{T}}_2 $$ ( wT 2 $$ {\mathrm{wT}}_2 $$ ) mapping for the characterization of diffuse and oncological liver diseases. METHODS: The proposed data acquisition consists of a magnetization preparation pulse and a two-echo gradient echo readout with a radial stack-of-stars trajectory, repeated with different preparations to achieve different T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ contrasts in a fixed acquisition time of 6 min. Regularized reconstruction was performed using self-navigation to account for motion during the free-breathing acquisition, followed by water-fat separation. Bloch simulations of the sequence were applied to optimize the sequence timing for B 1 $$ {B}_1 $$ insensitivity at 3 T, to correct for relaxation-induced blurring, and to map T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ using a dictionary. The proposed method was validated on a water-fat phantom with varying relaxation properties and in 10 volunteers against imaging and spectroscopy reference values. The performance and robustness of the proposed method were evaluated in five patients with abdominal pathologies. RESULTS: Simulations demonstrate good B 1 $$ {B}_1 $$ insensitivity of the proposed method in measuring T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ values. The proposed method produces co-registered wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ maps with a good agreement with reference methods (phantom: wT 1 = 1 . 02 wT 1,ref - 8 . 93 ms , R 2 = 0 . 991 $$ {\mathrm{wT}}_1=1.02\kern0.1em {\mathrm{wT}}_{1,\mathrm{ref}}-8.93\kern0.1em \mathrm{ms},{R}^2=0.991 $$ ; wT 2 = 1 . 03 wT 2,ref + 0 . 73 ms , R 2 = 0 . 995 $$ {\mathrm{wT}}_2=1.03\kern0.1em {\mathrm{wT}}_{2,\mathrm{ref}}+0.73\kern0.1em \mathrm{ms},{R}^2=0.995 $$ ). The proposed wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ mapping exhibits good repeatability and can be robustly performed in patients with pathologies. CONCLUSIONS: The proposed method allows whole-liver wT 1 $$ {\mathrm{wT}}_1 $$ and wT 2 $$ {\mathrm{wT}}_2 $$ quantification with high accuracy at isotropic resolution in a fixed acquisition time during free-breathing.
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PURPOSE: To investigate the effect of respiratory motion in terms of signal loss in prostate diffusion-weighted imaging (DWI), and to evaluate the usage of partial Fourier in a free-breathing protocol in a clinically relevant b-value range using both single-shot and multi-shot acquisitions. METHODS: A controlled breathing DWI acquisition was first employed at 3 T to measure signal loss from deep breathing patterns. Single-shot and multi-shot (2-shot) acquisitions without partial Fourier (no pF) and with partial Fourier (pF) factors of 0.75 and 0.65 were employed in a free-breathing protocol. The apparent SNR and ADC values were evaluated in 10 healthy subjects to measure if low pF factors caused low apparent SNR or overestimated ADC. RESULTS: Controlled breathing experiments showed a difference in signal coefficient of variation between shallow and deep breathing. In free-breathing single-shot acquisitions, the pF 0.65 scan showed a significantly (p < 0.05) higher apparent SNR than pF 0.75 and no pF in the peripheral zone (PZ) of the prostate. In the multi-shot acquisitions in the PZ, pF 0.75 had a significantly higher apparent SNR than 0.65 pF and no pF. The single-shot pF 0.65 scan had a significantly lower ADC than single-shot no pF. CONCLUSION: Deep breathing patterns can cause intravoxel dephasing in prostate DWI. For single-shot acquisitions at a b-value of 800 s/mm2, any potential risks of motion-related artefacts at low pF factors (pF 0.65) were outweighed by the increase in signal from a lower TE, as shown by the increase in apparent SNR. In multi-shot acquisitions however, the minimum pF factor should be larger, as shown by the lower apparent SNR at low pF factors.
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Partial Fourier encoding is popular in single-shot (ss) diffusion-weighted (DW) echo planar imaging (EPI) because it enables a shorter echo time (TE) and, hence, improves the signal-to-noise-ratio. Motion during diffusion encoding causes k-space shifting and dispersion, which compromises the quality of the homodyne reconstruction. This work provides a comprehensive understanding of the artifacts in homodyne reconstruction of partial Fourier ss-DW-EPI data in the presence of motion-induced phase and proposes the motion-induced phase-corrected homodyne (mpc-hdyne) reconstruction method to ameliorate these artifacts. Simulations with different types of motion-induced phase were performed to provide an understanding of the potential artifacts that occur in the homodyne reconstruction of partial Fourier ss-DW-EPI data. To correct for the artifacts, the mpc-hdyne reconstruction is proposed. The algorithm recenters k-space, updates the partial Fourier factor according to detected global k-space shifts, and removes low-resolution nonlinear phase before the conventional homodyne reconstruction. The mpc-hdyne reconstruction is tested on both simulation and in vivo data. Motion-induced phase can cause signal overestimation, worm artifacts, and signal loss in partial Fourier ss-DW-EPI data with the conventional homodyne reconstruction. Simulation and in vivo data showed that the proposed mpc-hdyne reconstruction ameliorated artifacts, yielding higher quality DW images compared with conventional homodyne reconstruction. Based on the understanding of the artifacts in homodyne reconstruction of partial Fourier ss-DW-EPI data, the mpc-hdyne reconstruction was proposed and showed superior performance compared with the conventional homodyne reconstruction on both simulation and in vivo data.
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Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Análise de Fourier , Fígado , Movimento (Física) , Humanos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Algoritmos , Artefatos , Simulação por Computador , Processamento de Imagem Assistida por Computador/métodosRESUMO
Cardiac motion causes unpredictable signal loss in respiratory-triggered diffusion-weighted magnetic resonance imaging (DWI) of the liver, especially inside the left lobe. The left liver lobe may thus be frequently neglected in the clinical evaluation of liver DWI. In this work, a data-driven algorithm that relies on the statistics of the signal in the left liver lobe to mitigate the motion-induced signal loss is presented. The proposed data-driven algorithm utilizes the exclusion of severely corrupted images with subsequent spatially dependent image scaling based on a signal-loss model to correctly combine the multi-average diffusion-weighted images. The signal in the left liver lobe is restored and the liver signal is more homogeneous after applying the proposed algorithm. Furthermore, overestimation of the apparent diffusion coefficient (ADC) in the left liver lobe is reduced. The proposed algorithm can therefore contribute to reduce the motion-induced bias in DWI of the liver and help to increase the diagnostic value of DWI in the left liver lobe.
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Artefatos , Fígado , Estudos Retrospectivos , Reprodutibilidade dos Testes , Fígado/diagnóstico por imagem , Movimento (Física) , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
PURPOSE: Evaluation of dual-layer spectral computed tomography (CT) for contrast enhancement during image-guided biopsy of liver lesions using virtual monoenergetic images (VMI) and virtual non-contrast (VNC) images. METHODS: Spectral CT data of 20 patients receiving CT-guided needle biopsy of focal liver lesions were used to generate VMI at energy levels from 40 to 200 keV and VNC images. Images were analyzed objectively regarding contrast-to-noise ratio between lesion center (CNRcent) or periphery (CNRperi) and normal liver parenchyma. Lesion visibility and image quality were evaluated on a 4-point Likert scale by two radiologists. RESULTS: Using VMI/VNC images, readers reported an increased visibility of the lesion compared to the conventional CT images in 18/20 cases. In 75% of cases, the highest visibility was derived by VMI-40. Showing all reconstructions simultaneously, VMI-40 offered the highest visibility in 75% of cases, followed by VNC in 12.5% of cases. Either CNRcent (17/20) or/and CNRperi (17/20) was higher (CNR increase > 50%) in 19/20 cases for VMI-40 or VNC images compared to conventional CT images. VMI-40 showed the highest CNRcent in 14 cases and the highest CNRperi in 12 cases. High image quality was present for all reconstructions with a minimum median of 3.5 for VMI-40 and VMI-50. CONCLUSIONS: When implemented in the CT scanner software, automated contrast enhancement of liver lesions during image-guided biopsy may facilitate the procedure.
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Neoplasias Hepáticas , Tomografia Computadorizada por Raios X , Humanos , Razão Sinal-Ruído , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Biópsia , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
The gadolinium-based contrast agent Gadoxetic acid and the platinum-based antitumor agent Cisplatin were quantitatively imaged in liver and liver cancer (hepatocellular carcinoma, HCC) tissue of rats by means of laser ablation-inductively coupled plasma-mass spectrometry. HCC bearing rats simultaneously received a tail vein injection of the hepatocyte-specific magnetic resonance imaging contrast agent Gadoxetic acid and a transarterial injection of Cisplatin 15 min before sacrifice and liver removal. Resecting HCC with adjacent liver tissue allows the comparison of Gd, Pt, and endogenous elements like Fe, Cu, and Zn in the various tissue types. Region of interest analysis reveals lower concentrations of Gd in HCC and higher Gd content in the adjacent liver, fitting the selective uptake of Gadoxetic acid into hepatocytes. Furthermore, two malignancy grades and their possible impact on the Gadoxetic acid and Cisplatin uptake are compared. For this, four high grade (G3) and two moderate grade (G2) HCCs were analysed, including a control sample each. Gd concentrations were lower in HCC irrespective of the grade of dedifferentiation (G2, G3) compared to adjacent liver. Despite local arterial Cisplatin injection, concentrations of Pt were similar or also reduced in HCC compared to liver tissue. In addition, endogenous Fe, Cu, and Zn were quantified. While Zn was homogenously distributed, higher Fe concentrations were determined in liver tissue compared to HCC. Hotspots of Cu suggest a deregulated copper homeostasis in certain liver lesions. The Gd and Fe distributions are compared in detail with cellular alterations examined by hematoxylin and eosin staining.
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OBJECTIVES: To examine the effect of high-b-value computed diffusion-weighted imaging (cDWI) on solid lesion detection and classification in pancreatic intraductal papillary mucinous neoplasm (IPMN), using endoscopic ultrasound (EUS) and histopathology as a standard of reference. METHODS: Eighty-two patients with known or suspected IPMN were retrospectively enrolled. Computed high-b-value images at b = 1000 s/mm2 were calculated from standard (b = 0, 50, 300, and 600 s/mm2) DWI images for conventional full field-of-view (fFOV, 3 × 3 × 4 mm3 voxel size) DWI. A subset of 39 patients received additional high-resolution reduced-field-of-view (rFOV, 2.5 × 2.5 × 3 mm3 voxel size) DWI. In this cohort, rFOV cDWI was compared against fFOV cDWI additionally. Two experienced radiologists evaluated (Likert scale 1-4) image quality (overall image quality, lesion detection and delineation, fluid suppression within the lesion). In addition, quantitative image parameters (apparent signal-to-noise ratio (aSNR), apparent contrast-to-noise ratio (aCNR), contrast ratio (CR)) were assessed. Diagnostic confidence regarding the presence/absence of diffusion-restricted solid nodules was assessed in an additional reader study. RESULTS: High-b-value cDWI at b = 1000 s/mm2 outperformed acquired DWI at b = 600 s/mm2 regarding lesion detection, fluid suppression, aCNR, CR, and lesion classification (p = < .001-.002). Comparing cDWI from fFOV and rFOV revealed higher image quality in high-resolution rFOV-DWI compared to conventional fFOV-DWI (p ≤ .001-.018). High-b-value cDWI images were rated non-inferior to directly acquired high-b-value DWI images (p = .095-.655). CONCLUSIONS: High-b-value cDWI may improve the detection and classification of solid lesions in IPMN. Combining high-resolution imaging and high-b-value cDWI may further increase diagnostic precision. CLINICAL RELEVANCE STATEMENT: This study shows the potential of computed high-resolution high-sensitivity diffusion-weighted magnetic resonance imaging for solid lesion detection in pancreatic intraductal papillary mucinous neoplasia (IPMN). The technique may enable early cancer detection in patients under surveillance. KEY POINTS: ⢠Computed high-b-value diffusion-weighted imaging (cDWI) may improve the detection and classification of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. ⢠cDWI calculated from high-resolution imaging increases diagnostic precision compared to cDWI calculated from conventional-resolution imaging. ⢠cDWI has the potential to strengthen the role of MRI for screening and surveillance of IPMN, particularly in view of the rising incidence of IPMNs combined with now more conservative therapeutic approaches.
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Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Razão Sinal-Ruído , Imagem de Difusão por Ressonância Magnética/métodos , PâncreasRESUMO
PURPOSE: To assess the effect of respiratory motion and cardiac driven pulsation in renal DWI and to examine asymmetrical velocity-compensated diffusion encoding waveforms for robust ADC mapping in the kidneys. METHODS: The standard monopolar Stejskal-Tanner pulsed gradient spin echo (pgse) and the asymmetric bipolar velocity-compensated (asym-vc) diffusion encoding waveforms were used for coronal renal DWI at 3T. The robustness of the ADC quantification in the kidneys was tested with the aforementioned waveforms in respiratory-triggered and breath-held cardiac-triggered scans at different trigger delays in 10 healthy subjects. RESULTS: The pgse waveform showed higher ADC values in the right kidney at short trigger delays in comparison to longer trigger delays in the respiratory triggered scans when the diffusion gradient was applied in the feet-head (FH) direction. The coefficient of variation over all respiratory trigger delays, averaged over all subjects was 0.15 for the pgse waveform in the right kidney when diffusion was measured in the FH direction; the corresponding coefficient of variation for the asym-vc waveform was 0.06. The effect of cardiac driven pulsation was found to be small in comparison to the effect of respiratory motion. CONCLUSION: Short trigger delays in respiratory-triggered scans can cause higher ADC values in comparison to longer trigger delays in renal DWI, especially in the right kidney when diffusion is measured in the FH direction. The asym-vc waveform can reduce ADC variation due to respiratory motion in respiratory-triggered scans at the cost of reduced SNR compared to the pgse waveform.
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Imagem de Difusão por Ressonância Magnética , Rim , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Movimento (Física) , Rim/diagnóstico por imagem , Coração/diagnóstico por imagem , Difusão , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To evaluate the perception of different types of AI-based assistance and the interaction of radiologists with the algorithm's predictions and certainty measures. METHODS: In this retrospective observer study, four radiologists were asked to classify Breast Imaging-Reporting and Data System 4 (BI-RADS4) lesions (n = 101 benign, n = 99 malignant). The effect of different types of AI-based assistance (occlusion-based interpretability map, classification, and certainty) on the radiologists' performance (sensitivity, specificity, questionnaire) were measured. The influence of the Big Five personality traits was analyzed using the Pearson correlation. RESULTS: Diagnostic accuracy was significantly improved by AI-based assistance (an increase of 2.8% ± 2.3%, 95 %-CI 1.5 to 4.0 %, p = 0.045) and trust in the algorithm was generated primarily by the certainty of the prediction (100% of participants). Different human-AI interactions were observed ranging from nearly no interaction to humanization of the algorithm. High scores in neuroticism were correlated with higher persuasibility (Pearson's r = 0.98, p = 0.02), while higher consciousness and change of accuracy showed an inverse correlation (Pearson's r = -0.96, p = 0.04). CONCLUSION: Trust in the algorithm's performance was mostly dependent on the certainty of the predictions in combination with a plausible heatmap. Human-AI interaction varied widely and was influenced by personality traits. KEY POINTS: ⢠AI-based assistance significantly improved the diagnostic accuracy of radiologists in classifying BI-RADS 4 mammography lesions. ⢠Trust in the algorithm's performance was mostly dependent on the certainty of the prediction in combination with a reasonable heatmap. ⢠Personality traits seem to influence human-AI collaboration. Radiologists with specific personality traits were more likely to change their classification according to the algorithm's prediction than others.
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Neoplasias da Mama , Doenças Vasculares , Humanos , Feminino , Estudos Retrospectivos , Algoritmos , Mamografia , Radiologistas , Neoplasias da Mama/diagnóstico por imagemRESUMO
BACKGROUND: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa). METHODS: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.4 and 4.8 in 10 healthy volunteers and 23 patients with histologically proven PCa. Image reconstructions using compressed SENSE (C-SENSE) and a combination of C-SENSE and DL-based artificial intelligence (C-SENSE AI) were analyzed. Qualitative image comparison was performed using a 6-point Likert scale (overall image quality, noise, motion artifacts, lesion detection, diagnostic certainty); the T2 and PI-RADS scores were compared between the two reconstructions. Additionally, quantitative image parameters were assessed (apparent SNR, apparent CNR, lesion size, line profiles). RESULTS: All C-SENSE AI-reconstructed images received a significantly higher qualitative rating compared to the C-SENSE standard images. Analysis of the quantitative parameters supported this finding, with significantly higher aSNR and aCNR. The line profiles demonstrated a significantly steeper signal change at the border of the prostatic lesion and the adjacent normal tissue in the C-SENSE AI-reconstructed images, whereas the T2 and PI-RADS scores as well as the lesion size did not differ. CONCLUSION: In this prospective study, we demonstrated the clinical feasibility of a novel C-SENSE AI reconstruction enabling a 58% acceleration in T2w imaging of the prostate while obtaining significantly better image quality.
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Background: Quantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF. Methods: In this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (N=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (N=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF. Results: Prior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (ΔPDFF=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (ΔPDFF=2.1 ± 2.5%, P=0.03). There was no significant change in T2* (ΔT2*=1.7 ± 1.1ms vs. ΔT2*=1.1 ± 1.3ms, P=0.31) and BMD (ΔBMD=-1.2 ± 11.3mg/cm3 vs. ΔBMD=-11.4 ± 24.1mg/cm3, P= 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (P=0.66, P=0.35 and P= 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60). Conclusions: In our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.
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Fraturas por Compressão , Fraturas da Coluna Vertebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Prótons , Medula Óssea/diagnóstico por imagem , Fraturas por Compressão/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , ÁguaRESUMO
Background: Proton-density fat fraction (PDFF) and T2* of the vertebrae, as well as the cross-sectional area (CSA) of the paraspinal musculature (PSM), have been suggested as biomarkers for bone fragility. The aim of this study was to longitudinally assess changes in PDFF, T2* and CSA of the PSM over 6 months in patients with and without osteoporosis. Methods: Opportunistic bone mineral density (BMD) measurements (BMD < 120 mg/cm3) were obtained from a CT acquired during the clinical routine work up in osteoporotic/osteopenic patients (n = 29, mean age 72.37 ± 10.12 years, 16 women). These patients were frequency-matched for age and sex to subjects with normal BMD values (n = 29). All study patients underwent 3T MR imaging at baseline and 6-month follow up, including spoiled gradient echo sequences for chemical shift encoding-based water-fat separation, from which T2* and PDFF values of the lumbar spine and the PSM were obtained. Moreover, the CSA of the PSM was assessed longitudinally. Changes in T2*, PDFF and CSA over 6 months were calculated for the vertebrae and PSM and associations with baseline BMD values were assessed. Results: The change in CSA of the PSM over 6 months was significantly lower in the osteoporotic/osteopenic group (−91.5 ± 311.7 mm2), compared to the non-osteoporotic group, in which the CSA increased (29.9 ± 164.0 mm2, p = 0.03). In a further analysis, patients with higher vertebral PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower vertebral PDFF at baseline (0.9 ± 1.6 ms vs. 0.0 ± 1.8 ms, p = 0.04). Moreover, patients with higher PSM PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower PSM PDFF at baseline (0.9 ± 2.0 ms vs. 0.0 ± 1.3 ms, p = 0.03). Conclusion: The PSM CSA decreased significantly longitudinally in patients with osteoporosis/osteopenia, compared to those without. Additionally, higher vertebral and PSM PDFF at baseline were associated with stronger changes in vertebral bone marrow T2*. Therefore, longitudinal PDFF and T2* mapping may be useful quantitative radiation-free tools for the assessment and prediction of muscle and bone health in patients with suspected osteoporosis/osteopenia.
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PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a molecularly heterogeneous tumor entity with no clinically established imaging biomarkers. We hypothesize that tumor morphology and physiology, including vascularity and perfusion, show variations that can be detected by differences in contrast agent (CA) accumulation measured non-invasively. This work seeks to establish imaging biomarkers for tumor stratification and therapy response monitoring in PDAC, based on this hypothesis. METHODS AND MATERIALS: Regional CA accumulation in PDAC was correlated with tumor vascularization, stroma content, and tumor cellularity in murine and human subjects. Changes in CA distribution in response to gemcitabine (GEM) were monitored longitudinally with computed tomography (CT) Hounsfield Units ratio (HUr) of tumor to the aorta or with magnetic resonance imaging (MRI) ΔR1 area under the curve at 60 s tumor-to-muscle ratio (AUC60r). Tissue analyses were performed on co-registered samples, including endothelial cell proliferation and cisplatin tissue deposition as a surrogate of chemotherapy delivery. RESULTS: Tumor cell poor, stroma-rich regions exhibited high CA accumulation both in human (meanHUr 0.64 vs. 0.34, p < 0.001) and mouse PDAC (meanAUC60r 2.0 vs. 1.1, p < 0.001). Compared to the baseline, in vivo CA accumulation decreased specifically in response to GEM treatment in a subset of human (HUr -18%) and mouse (AUC60r -36%) tumors. Ex vivo analyses of mPDAC showed reduced cisplatin delivery (GEM: 0.92 ± 0.5 mg/g, vs. vehicle: 3.1 ± 1.5 mg/g, p = 0.004) and diminished endothelial cell proliferation (GEM: 22.3% vs. vehicle: 30.9%, p = 0.002) upon GEM administration. CONCLUSION: In PDAC, CA accumulation, which is related to tumor vascularization and perfusion, inversely correlates with tumor cellularity. The standard of care GEM treatment results in decreased CA accumulation, which impedes drug delivery. Further investigation is warranted into potentially detrimental effects of GEM in combinatorial therapy regimens.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Cisplatino/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Biomarcadores , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética , Tomografia , Linhagem Celular Tumoral , Gencitabina , Neoplasias PancreáticasRESUMO
BACKGROUND: Our purpose was to investigate the potential of high-resolution, high b-value computed DWI (cDWI) in pancreatic ductal adenocarcinoma (PDAC) detection. MATERIALS AND METHODS: We retrospectively enrolled 44 patients with confirmed PDAC. Respiratory-triggered, diffusion-weighted, single-shot echo-planar imaging (ss-EPI) with both conventional (i.e., full field-of-view, 3 × 3 × 4 mm voxel size, b = 0, 50, 300, 600 s/mm2) and high-resolution (i.e., reduced field-of-view, 2.5 × 2.5 × 3 mm voxel size, b = 0, 50, 300, 600, 1000 s/mm2) imaging was performed for suspected PDAC. cDWI datasets at b = 1000 s/mm2 were generated for the conventional and high-resolution datasets. Three radiologists were asked to subjectively rate (on a Likert scale of 1-4) the following metrics: image quality, lesion detection and delineation, and lesion-to-pancreas intensity relation. Furthermore, the following quantitative image parameters were assessed: apparent signal-to-noise ratio (aSNR), contrast-to-noise ratio (aCNR), and lesion-to-pancreas contrast ratio (CR). RESULTS: High-resolution, high b-value computed DWI (r-cDWI1000) enabled significant improvement in lesion detection and a higher incidence of a high lesion-to-pancreas intensity relation (type 1, clear hyperintense) compared to conventional high b-value computed and high-resolution high b-value acquired DWI (f-cDWI1000 and r-aDWI1000, respectively). Image quality was rated inferior in the r-cDWI1000 datasets compared to r-aDWI1000. Furthermore, the aCNR and CR were higher in the r-cDWI1000 datasets than in f-cDWI1000 and r-aDWI1000. CONCLUSION: High-resolution, high b-value computed DWI provides significantly better visualization of PDAC compared to the conventional high b-value computed and high-resolution high b-value images acquired by DWI.
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Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Humanos , Organoides/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Medicina de Precisão , Neoplasias PancreáticasRESUMO
OBJECTIVE : To experimentally characterize the effectiveness of a gradient nonlinearity correction method in removing ADC bias for different motion-compensated diffusion encoding waveforms. METHODS: The diffusion encoding waveforms used were the standard monopolar Stejskal-Tanner pulsed gradient spin echo (pgse) waveform, the symmetric bipolar velocity-compensated waveform (sym-vc), the asymmetric bipolar velocity-compensated waveform (asym-vc) and the asymmetric bipolar partial velocity-compensated waveform (asym-pvc). The effectiveness of the gradient nonlinearity correction method using the spherical harmonic expansion of the gradient coil field was tested with the aforementioned waveforms in a phantom and in four healthy subjects. RESULTS: The gradient nonlinearity correction method reduced the ADC bias in the phantom experiments for all used waveforms. The range of the ADC values over a distance of ± 67.2 mm from isocenter reduced from 1.29 × 10-4 to 0.32 × 10-4 mm2/s for pgse, 1.04 × 10-4 to 0.22 × 10-4 mm2/s for sym-vc, 1.22 × 10-4 to 0.24 × 10-4 mm2/s for asym-vc and 1.07 × 10-4 to 0.11 × 10-4 mm2/s for asym-pvc. The in vivo results showed that ADC overestimation due to motion or bright vessels can be increased even further by the gradient nonlinearity correction. CONCLUSION: The investigated gradient nonlinearity correction method can be used effectively with various motion-compensated diffusion encoding waveforms. In coronal liver DWI, ADC errors caused by motion and residual vessel signal can be increased even further by the gradient nonlinearity correction.
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Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Movimento (Física)RESUMO
OBJECTIVES: To prospectively evaluate an L1 regularized iterative SENSE reconstruction (L1-R SENSE) to eliminate band-like artifacts frequently seen with parallel imaging (SENSE) at high acceleration factors in high resolution diffusion weighted magnetic resonance imaging of the pancreas. METHODS: Fourteen patients with pancreatic ductal adenocarcinoma (PDAC) underwent respiratory triggered DWI ss-EPI at a resolution of 2.5 × 2.5 × 3 mm3 with uniform undersampling in the phase encoding direction (AP axis) with an acceleration factor of 4. Data were reconstructed using the standard SENSE reconstruction routine of the vendor and an iterative SENSE reconstruction employing L1 regularization after a wavelet sparsifying transformation (L1-R SENSE). Retrospective reconstruction of the data with a lower number of averages was performed using both reconstruction methods. Two radiologists independently assessed noise artifacts, anatomical details and image quality (IQ) subjectively with a 4-point scale. Apparent diffusion coefficient (ADC) and covariance (CV) of ADC estimated from images reconstructed at a different number of averages for PDAC and the normal pancreas were assessed. RESULTS: L1-R SENSE resulted in higher IQ and less noise artifacts than SENSE. Anatomical details were significantly higher for SENSE in one reader. Mean ADC of PDAC and normal pancreas were significantly higher for L1-R SENSE than SENSE. L1-R SENSE revealed lower CV of ADC for normal pancreas compared to SENSE, whereas no difference was noted for PDAC. CONCLUSION: Compared with traditional SENSE reconstruction, L1-R SENSE effectively reduces band-like noise and improves the robustness of the ADC estimation from acquisitions using single-shot DW-EPI of the pancreas.
Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Artefatos , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Humanos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time. METHODS: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section. RESULTS: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = -0.55, p < 0.01) and baseline psoas PDFF (r = -0.52, p = 0.02) with maximum BMI change during the course of the disease. CONCLUSION: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.
RESUMO
PURPOSE: In this prospective exploratory study, we evaluated the feasibility of [18F]fluorodeoxyglucose ([18F]FDG) PET/MRI-based chemotherapy response prediction in pancreatic ductal adenocarcinoma at two weeks upon therapy onset. MATERIAL AND METHODS: In a mixed cohort, seventeen patients treated with chemotherapy in neoadjuvant or palliative intent were enrolled. All patients were imaged by [18F]FDG PET/MRI before and two weeks after onset of chemotherapy. Response per RECIST1.1 was then assessed at 3 months [18F]FDG PET/MRI-derived parameters (MTV50%, TLG50%, MTV2.5, TLG2.5, SUVmax, SUVpeak, ADCmax, ADCmean and ADCmin) were assessed, using multiple t-test, Man-Whitney-U test and Fisher's exact test for binary features. RESULTS: At 72 ± 43 days, twelve patients were classified as responders and five patients as non-responders. An increase in ∆MTV50% and ∆ADC (≥ 20% and 15%, respectively) and a decrease in ∆TLG50% (≤ 20%) at 2 weeks after chemotherapy onset enabled prediction of responders and non-responders, respectively. Parameter combinations (∆TLG50% and ∆ADCmax or ∆MTV50% and ∆ADCmax) further improved discrimination. CONCLUSION: Multiparametric [18F]FDG PET/MRI-derived parameters, in particular indicators of a change in tumor glycolysis and cellularity, may enable very early chemotherapy response prediction. Further prospective studies in larger patient cohorts are recommended to their clinical impact.
RESUMO
BACKGROUND: Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology. AIM: To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone. METHODS: In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests. RESULTS: Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001). CONCLUSION: Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.