Publications by authors named "Jochen Keupp"

34 Publications

Prospective acceleration of parallel RF transmission-based 3D chemical exchange saturation transfer imaging with compressed sensing.

Magn Reson Med 2019 11 17;82(5):1812-1821. Epub 2019 Jun 17.

Divison of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland.

Purpose: To develop prospectively accelerated 3D CEST imaging using compressed sensing (CS), combined with a saturation scheme based on time-interleaved parallel transmission.

Methods: A variable density pseudo-random sampling pattern with a centric elliptical k-space ordering was used for CS acceleration in 3D. Retrospective CS studies were performed with CEST phantoms to test the reconstruction scheme. Prospectively CS-accelerated 3D-CEST images were acquired in 10 healthy volunteers and 6 brain tumor patients with an acceleration factor (R ) of 4 and compared with conventional SENSE reconstructed images. Amide proton transfer weighted (APTw) signals under varied RF saturation powers were compared with varied acceleration factors.

Results: The APTw signals obtained from the CS with acceleration factor of 4 were well-preserved as compared with the reference image (SENSE R = 2) both in retrospective phantom and prospective healthy volunteer studies. In the patient study, the APTw signals were significantly higher in the tumor region (gadolinium [Gd]-enhancing tumor core) than in the normal tissue (p < .001). There was no significant APTw difference between the CS-accelerated images and the reference image. The scan time of CS-accelerated 3D APTw imaging was dramatically reduced to 2:10 minutes (in-plane spatial resolution of 1.8 1.8 mm ; 15 slices with 4-mm slice thickness) as compared with SENSE (4:07 minutes).

Conclusion: Compressed sensing acceleration was successfully extended to 3D-CEST imaging without compromising CEST image quality and quantification. The CS-based CEST imaging can easily be integrated into clinical protocols and would be beneficial for a wide range of applications.
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http://dx.doi.org/10.1002/mrm.27875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660350PMC
November 2019

Histogram analysis of amide proton transfer-weighted imaging: comparison of glioblastoma and solitary brain metastasis in enhancing tumors and peritumoral regions.

Eur Radiol 2019 Aug 28;29(8):4133-4140. Epub 2018 Nov 28.

Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.

Objectives: Differentiation of glioblastomas (GBMs) and solitary brain metastases (SBMs) is an important clinical problem. The aim of this study was to determine whether amide proton transfer-weighted (APTW) imaging is useful for distinguishing GBMs from SBMs.

Methods: We examined 31 patients with GBM and 17 with SBM. For each tumor, enhancing areas (EAs) and surrounding non-enhancing areas with T2-prolongation (peritumoral high signal intensity areas, PHAs) were manually segmented using fusion images of the post-contrast T1-weighted and T2-weighted images. The mean amide proton transfer signal intensities (APTSIs) were compared among the EAs, PHAs, and contralateral normal appearing white matter (NAWM) within each tumor type. Furthermore, we analyzed APTSI histograms to compare the EAs and PHAs of GBMs and SBMs.

Results: In GBMs, the mean APTSI in EAs (2.92 ± 0.74%) was the highest, followed by that in PHAs (1.64 ± 0.83%, p < 0.001) and NAWM (0.43 ± 0.83%, p < 0.001). In SBMs, the mean APTSI in EAs (1.85 ± 0.99%) and PHAs (1.42 ± 0.45%) were significantly higher than that in NAWM (0.42 ± 0.30%, p < 0.001), whereas no significant difference was found between EAs and PHAs. The mean and 10th, 25th, 50th, 75th, and 90th percentiles for APT in EAs of GBMs were significantly higher than those of SBMs. However, no significant difference was found between GBMs and SBMs in any histogram parameters for PHA.

Conclusions: APTSI in EAs, but not PHAs, is useful for differentiation between GBMs and SBMs.

Key Points: • Amide proton transfer-weighted imaging and histogram analysis in the enhancing tumor can provide useful information for differentiation between glioblastomas and solitary brain metastasis. • Amide proton transfer signal intensity histogram parameters from peritumoral areas showed no significant difference between glioblastomas and solitary brain metastasis. • Vasogenic edema alone can substantially increase amide proton transfer signal intensity which may mimic tumor invasion.
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http://dx.doi.org/10.1007/s00330-018-5832-1DOI Listing
August 2019

Accelerating chemical exchange saturation transfer MRI with parallel blind compressed sensing.

Magn Reson Med 2019 01 26;81(1):504-513. Epub 2018 Aug 26.

Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Purpose: Chemical exchange saturation transfer is a novel and promising MRI contrast method, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced quality of CEST. Here, parallel blind compressed sensing (PBCS), combining blind compressed sensing (BCS) and parallel imaging, is evaluated for the acceleration of CEST in brain and breast.

Methods: The CEST data were collected in phantoms, brain (N = 3), and breast (N = 2). Retrospective Cartesian undersampling was implemented and the reconstruction results of PBCS-CEST were compared with BCS-CEST and k-t sparse-SENSE CEST. The normalized RMSE and the high-frequency error norm were used for quantitative comparison.

Results: In phantom and in vivo brain experiments, the acceleration factor of R = 10 (24 k-space lines) was achieved and in breast R = 5 (30 k-space lines), without compromising the quality of the PBCS-reconstructed magnetization transfer rate asymmetry maps and Z-spectra. Parallel BCS provides better reconstruction quality when compared with BCS, k-t sparse-SENSE, and SENSE methods using the same number of samples. Parallel BCS overperforms BCS, indicating that the inclusion of coil sensitivity improves the reconstruction of the CEST data.

Conclusion: The PBCS method accelerates CEST without compromising its quality. Compressed sensing in combination with parallel imaging can provide a valuable alternative to parallel imaging alone for accelerating CEST experiments.
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http://dx.doi.org/10.1002/mrm.27400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497066PMC
January 2019

Amide proton transfer imaging to predict tumor response to neoadjuvant chemotherapy in locally advanced rectal cancer.

J Gastroenterol Hepatol 2019 Jan 2;34(1):140-146. Epub 2018 Jul 2.

Department of Clinical Radiology, Kyushu University, Fukuoka, Japan.

Background And Aim: The amount of proteins and peptides can be estimated with amide proton transfer (APT) imaging. Previous studies demonstrated the usefulness of APT imaging to predict tumor malignancy. We determined whether APT imaging can predict the tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC).

Methods: Seventeen patients with LARC who underwent a pretherapeutic magnetic resonance examination including APT imaging and NAC (at least two courses) were enrolled. The APT-weighted imaging (WI) signal intensity (SI) (%) was defined as magnetization transfer ratio asymmetry (MTR ) at the offset of 3.5 ppm. Each tumor was histologically evaluated for the degree of degeneration and necrosis and then classified as one of five histological Grades (0, none; 1a, less than 1/3; 1b, 1/3 to 2/3; 2, more than 2/3; 3, all). We compared the mean APTWI SIs of the tumors between the Grade 0/1a/1b (low-response group) and Grade 2/3 (high-response group) by Student's t-test. We used receiver operating characteristics curves to determine the diagnostic performance of the APTWI SI for predicting the tumor response.

Results: The mean APTWI SI of the low-response group (n = 12; 3.05 ± 1.61%) was significantly higher than that of the high-response group (n = 5; 1.14 ± 1.13%) (P = 0.029). The area under the curve for predicting the tumor response using the APTWI SI was 0.87. When ≥2.75% was used as an indicator of low-response status, 75% sensitivity and 100% specificity of the APTWI SI were obtained.

Conclusion: Pretherapeutic APT imaging can predict the tumor response to NAC in patients with LARC.
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http://dx.doi.org/10.1111/jgh.14315DOI Listing
January 2019

Amide proton transfer imaging can predict tumor grade in rectal cancer.

Magn Reson Imaging 2018 09 2;51:96-103. Epub 2018 May 2.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Purpose: To prospectively investigate the ability of amide proton transfer (APT) imaging, in comparison with that of diffusion-weighted imaging (DWI), to predict pathological factors in rectal cancer.

Materials And Methods: Twenty-two patients who underwent MR examination including APT imaging and DWI for evaluation of rectal cancer were enrolled. APT signal intensity (SI) was defined as the magnetization transfer asymmetry at 3.5 ppm and was mapped. An apparent diffusion coefficient (ADC) map was generated using b-values of 0, 500 and 1000 s/mm. APT SI and ADC were calculated by placing regions-of-interest in the tumors on these maps. Pathological factors including tumor size and tumor grade were also evaluated. Average APT SIs or ADCs were compared between the two groups classified based on each pathological factor using Student's t-test.

Results: The average APT SI of tumors with diameters of 5 cm or more (3.09 ± 1.41%) was significantly higher than that of tumors with diameters < 5 cm (1.83 ± 1.38%). In addition, the average APT SI of moderately differentiated adenocarcinoma (2.82 ± 1.51%) was significantly higher than that of well-differentiated adenocarcinoma (1.24 ± 0.57%). There was no difference in ADC between groups classified based on any pathological factor.

Conclusion: Amide proton transfer imaging can predict tumor grade in rectal cancer.
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http://dx.doi.org/10.1016/j.mri.2018.04.017DOI Listing
September 2018

Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography.

Eur Radiol 2018 Aug 27;28(8):3285-3295. Epub 2018 Feb 27.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas.

Materials And Methods: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNR and APT) and 90% histogram values (TNR90 and APT90).

Results: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APT (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNR (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05).

Conclusions: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism.

Key Points: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.
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http://dx.doi.org/10.1007/s00330-018-5341-2DOI Listing
August 2018

CEST-Dixon for human breast lesion characterization at 3 T: A preliminary study.

Magn Reson Med 2018 09 10;80(3):895-903. Epub 2018 Jan 10.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

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http://dx.doi.org/10.1002/mrm.27079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980671PMC
September 2018

Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.

Radiology 2018 03 30;286(3):909-917. Epub 2017 Oct 30.

From the Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan (Y.T.); Departments of Clinical Radiology (Y.T., A.N., O.T., K.I., Y.U., D.O., N.F., H.H.), Advanced Imaging and Interventional Radiology (Y.A.), Gynecology and Obstetrics (K.S.), and Anatomic Pathology (T.H., Y.O.), Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan; and Philips Research, Hamburg, Germany (J.K.).

Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10 mm/sec ± 0.2, and 0.6 × 10 mm/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10 mm/sec ± 0.1, and 0.5 × 10 mm/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10 mm/sec ± 0.1, and 0.5 × 10 mm/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. RSNA, 2017 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2017170349DOI Listing
March 2018

Z-spectrum appearance and interpretation in the presence of fat: Influence of acquisition parameters.

Magn Reson Med 2018 05 1;79(5):2731-2737. Epub 2017 Sep 1.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Purpose: Chemical exchange saturation transfer (CEST) MRI is increasingly evolving from brain to body applications. One of the known problems in the body imaging is the presence of strong lipid signals. Although their influence on the CEST effect is acknowledged, there was no study that focuses on the interplay among echo time, fat fraction, and Z-spectrum. This study strives to address these points, with the emphasis on the application in the breast.

Methods: Z-spectra were simulated in phase and out of phase of the main fat peak at -3.4 ppm, with the fat fraction varying from 0 to 100%. The magnetization transfer ratio asymmetry in two ranges, centering at the exchanging pool and at 3.5 ppm approximately opposite the nonexchanging fat pool, were calculated and were plotted against fat fraction. The results were verified in phantoms and in vivo.

Results: The results demonstrate the combined influence of fat fraction and echo time on the Z-spectrum for gradient echo based CEST acquisitions. The influence is straightforward in the in-phase images, but it is more complicated in the out-of-phase images, potentially leading to erroneous CEST contrast.

Conclusions: This study provides a basis for understanding the origin and appearance of lipid artifacts in CEST imaging, and lays the foundation for their efficient removal. Magn Reson Med 79:2731-2737, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821535PMC
May 2018

Interleaved Mapping of Temperature and Longitudinal Relaxation Rate to Monitor Drug Delivery During Magnetic Resonance-Guided High-Intensity Focused Ultrasound-Induced Hyperthermia.

Invest Radiol 2017 10;52(10):620-630

From the *Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven; †Philips Research, Eindhoven, the Netherlands; ‡Department of Radiology, Experimental Imaging and Image-guided Therapy, University Hospital of Cologne, Cologne; and §Philips Research, Hamburg, Germany.

Objectives: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a method to heat lesions noninvasively to a stable, elevated temperature and a well-suited method to induce local hyperthermia (41°C-43°C) in deep-seated tissues. Magnetic Resonance (MR) imaging provides therapy planning on anatomical images and offers temperature feedback based on near-real-time MR thermometry. Although constant acquisition of MR thermometry data is crucial to ensure prolonged hyperthermia, it limits the freedom to perform measurements of other MR parameters, which are of interest during hyperthermia treatments. In image-guided drug delivery applications, co-encapsulation of paramagnetic MR contrast agents with a drug inside temperature-sensitive liposomes (TSLs) allows to visualize hyperthermia-triggered drug delivery through changes of the longitudinal relaxation rate R1. While the drug accumulates in the heated tumor tissue, R1 changes can be used for an estimate of the tumor drug concentration. The main objective of this study was to demonstrate that interleaved MR sequences are able to monitor temperature with an adequate temporal resolution and could give a reasonable estimate of the achieved tumor drug concentration through R1 changes. To this aim, in vitro validation tests and an in vivo proof-of-concept study were performed.

Materials And Methods: All experiments were performed on a clinical 3-T MR-HIFU system adapted with a preclinical setup. The validity of the R1 values and the temperature maps stability were evaluated in phantom experiments and in ex vivo porcine muscle tissue. In vivo experiments were performed on rats bearing a 9L glioma tumor on their hind limb. All animals (n = 4 HIFU-treated, n = 4 no HIFU) were injected intravenously with TSLs co-encapsulating doxorubicin and gadoteridol as contrast agent. The TSL injection was followed by either 2 times 15 minutes of MR-HIFU-induced hyperthermia or a sham treatment. R1 maps were acquired before, during, and after sonication, using a single slice Inversion Recovery Look-Locker (IR-LL) sequence (field of view [FOV], 50 × 69 mm; in-plane resolution, 0.52 × 0.71 mm; slice thickness, 3 mm; 23 phases of 130 milliseconds; 1 full R1 map every 2 minutes). The R1 maps acquired during treatment were interleaved with 2 perpendicular proton resonance frequency shift (PRFS) MR thermometry slices (dynamic repetition time, 8.6 seconds; FOV, 250 × 250 mm; 1.4 × 1.4 mm in-plane resolution; 4 mm slice thickness). Tumor doxorubicin concentrations were determined fluorometrically.

Results: In vitro results showed a slight but consistent overestimation of the measured R1 values compared with calibrated R1 values, regardless whether the R1 was acquired with noninterleaved IR-LL or interleaved. The average treatment cell temperature had a slightly higher temporal standard deviation for the interleaved PRFS sequence compared with the noninterleaved PRFS sequence (0.186°C vs 0.101°C, respectively). The prolonged time in between temperature maps due to the interleaved IR-LL sequence did not degrade the temperature stability during MR-HIFU treatment (Taverage = 40.9°C ± 0.3°C). Upon heat treatment, some tumors showed an R1 increase in a large part of the tumor while other tumors hardly showed any ΔR1. The tumor doxorubicin concentration showed a linear correlation with the average ΔR1 during both sonications (n = 8, Radj = 0.933), which was higher than for the ΔR1 measured after tumor cooldown (averaged for both sonications, n = 8, Radj = 0.877).

Conclusions: The new approach of interleaving different MR sequences was applied to simultaneously acquire R1 maps and PRFS thermometry scans during a feedback-controlled MR-HIFU-induced hyperthermia treatment. Interleaved acquisition did not compromise speed or accuracy of each scan. The ΔR1 acquired during treatment was used to visualize and quantify hyperthermia-triggered release of gadoteridol from TSLs and better reflected the intratumoral doxorubicin concentrations than the ΔR1 measured after cooldown of the tumor, exemplifying the benefit of interleaving R1 maps with temperature maps during drug delivery. Our study serves as an example for interleaved MR acquisition schemes, which introduce a higher flexibility in speed, sequence optimization, and timing.
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http://dx.doi.org/10.1097/RLI.0000000000000392DOI Listing
October 2017

Anti-angiogenic Nanotherapy Inhibits Airway Remodeling and Hyper-responsiveness of Dust Mite Triggered Asthma in the Brown Norway Rat.

Theranostics 2017 1;7(2):377-389. Epub 2017 Jan 1.

Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αβ-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Anti-neovascular effectiveness of αβ-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0.01) in the upper airways/bronchi of HDM rats using simultaneous F/H MR neovascular imaging, which was corroborated by adjunctive fluorescent microscopy. Micelles without a drug payload (αβ-No-Drug) served as a carrier-only control. Morphometric measurements of HDM rat airway size (perimeter) and vessel number at 21d revealed classic vascular expansion in control rats but less vascularity (p<0.001) after the anti-angiogenic nanotherapies. CD31 RNA expression independently corroborated the decrease in airway microvasculature. Methacholine (MCh) induced respiratory system resistance (Rrs) was high in the HDM rats receiving αβ-No-Drug micelles while αβ-Dxtl-PD or αβ-Fum-PD micelles markedly and equivalently attenuated airway hyper-responsiveness and improved airway compliance. Total inflammatory BAL cells among HDM challenged rats did not differ with treatment, but αβ macrophages/monocytes were significantly reduced by both nanotherapies (p<0.001), most notably by the αβ-Dxtl-PD micelles. Additionally, αβ-Dxtl-PD decreased BAL eosinophil and αβ CD45 leukocytes relative to αβ-No-Drug micelles, whereas αβ-Fum-PD micelles did not. These results demonstrate the potential of targeted anti-angiogenesis nanotherapy to ameliorate the inflammatory hallmarks of asthma in a clinically relevant rodent model.
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http://dx.doi.org/10.7150/thno.16627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5197071PMC
October 2017

Balanced Steady-State Free Precession (bSSFP) from an effective field perspective: Application to the detection of chemical exchange (bSSFPX).

J Magn Reson 2017 Feb 8;275:55-67. Epub 2016 Dec 8.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

Chemical exchange saturation transfer (CEST) is a novel contrast mechanism and it is gaining increasing popularity as many promising applications have been proposed and investigated. Fast and quantitative CEST imaging techniques are further needed in order to increase the applicability of CEST for clinical use as well as to derive quantitative physiological and biological information. Steady-state methods for fast CEST imaging have been reported recently. Here, we observe that an extreme case of these methods is a balanced steady-state free precession (bSSFP) sequence. The bSSFP in itself is sensitive to the exchange processes; hence, no additional saturation or preparation is needed for CEST-like data acquisition. The bSSFP experiment can be regarded as observation during saturation, without separate saturation and acquisition modules as used in standard CEST and similar experiments. One of the differences from standard CEST methods is that the bSSFP spectrum is an XY-spectrum not a Z-spectrum. As the first proof-of-principle step, we have implemented the steady-state bSSFP sequence for chemical exchange detection (bSSFPX) and verified its feasibility in phantom studies. These studies have shown that bSSFPX can achieve exchange-mediated contrast comparable to the standard CEST experiment. Therefore, the bSSFPX method has a potential for fast and quantitative CEST data acquisition.
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http://dx.doi.org/10.1016/j.jmr.2016.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810596PMC
February 2017

Amide proton transfer imaging of brain tumors using a self-corrected 3D fast spin-echo dixon method: Comparison With separate B correction.

Magn Reson Med 2017 06 6;77(6):2272-2279. Epub 2016 Jul 6.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Purpose: To assess the quantitative performance of three-dimensional (3D) fast spin-echo (FSE) Dixon amide proton transfer (APT) imaging of brain tumors compared with B correction with separate mapping methods.

Methods: Twenty-two patients with brain tumors (54.2 ± 18.7 years old, 12 males and 10 females) were scanned at 3 Tesla (T). Z-spectra were obtained at seven different frequency offsets at ±3.1 ppm, ± 3.5 ppm, ± 3.9 ppm, and -1560 ppm. The scan was repeated three times at +3.5 ppm with echo shifts for Dixon B mapping. The APT image corrected by a three-point Dixon-type B map from the same scan (3D-Dixon) or a separate B map (2D-separate and 3D-separate), and an uncorrected APT image (3D-uncorrected) were generated. We compared the APT-weighted signals within a tumor obtained with each 3D method with those obtained with 2D-separate as a reference standard.

Results: Excellent agreements and correlations with the 2D-separate were obtained by the 3D-Dixon method for both mean (ICC = 0.964, r = 0.93, P < 0.0001) and 90th-percentile (ICC = 0.972, r = 0.95, P < 0.0001) APT-weighted signals. These agreements and correlations for 3D-Dixon were better than those obtained by the 3D-uncorrected and 3D-separate methods.

Conclusion: The 3D FSE Dixon APT method with intrinsic B correction offers a quantitative performance that is similar to that of established two-dimensional (2D) methods. Magn Reson Med 77:2272-2279, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26322DOI Listing
June 2017

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

J Magn Reson Imaging 2017 01 7;45(1):125-131. Epub 2016 Jul 7.

Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA.

Purpose: To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate.

Materials And Methods: Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system.

Results: The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI.

Conclusion: The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm .

Level Of Evidence: 4 J. Magn. Reson. Imaging 2017;45:125-131.
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http://dx.doi.org/10.1002/jmri.25353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364696PMC
January 2017

Amide Proton Transfer Imaging of Diffuse Gliomas: Effect of Saturation Pulse Length in Parallel Transmission-Based Technique.

PLoS One 2016 26;11(5):e0155925. Epub 2016 May 26.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.

In this study, we evaluated the dependence of saturation pulse length on APT imaging of diffuse gliomas using a parallel transmission-based technique. Twenty-two patients with diffuse gliomas (9 low-grade gliomas, LGGs, and 13 high-grade gliomas, HGGs) were included in the study. APT imaging was conducted at 3T with a 2-channel parallel transmission scheme using three different saturation pulse lengths (0.5 s, 1.0 s, 2.0 s). The 2D fast spin-echo sequence was used for imaging. Z-spectrum was obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. Magnetization transfer ratio (MTRasym) and ΔMTRasym (contrast between tumor and normal white matter) at 3.5 ppm were compared among different saturation lengths. A significant increase in MTRasym (3.5 ppm) of HGG was found when the length of saturation pulse became longer (3.09 ± 0.54% at 0.5 s, 3.83 ± 0.67% at 1 s, 4.12 ± 0.97% at 2 s), but MTRasym (3.5 ppm) was not different among the saturation lengths in LGG. ΔMTRasym (3.5 ppm) increased with the length of saturation pulse in both LGG (0.48 ± 0.56% at 0.5 s, 1.28 ± 0.56% at 1 s, 1.88 ± 0.56% at 2 s and HGG (1.72 ± 0.54% at 0.5 s, 2.90 ± 0.49% at 1 s, 3.83 ± 0.88% at 2 s). In both LGG and HGG, APT-weighted contrast was enhanced with the use of longer saturation pulses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881971PMC
July 2017

Recent Advances in Fluorine Magnetic Resonance Imaging with Perfluorocarbon Emulsions.

Engineering (Beijing) 2015 Dec 16;1(4):475-489. Epub 2016 Mar 16.

Division of Cardiology, Washington University School of Medical, St. Louis, MO 63110, USA.

The research roots of fluorine (F) magnetic resonance imaging (MRI) date back over 35 years. Over that time span, H imaging flourished and was adopted worldwide with an endless array of applications and imaging approaches, making magnetic resonance an indispensable pillar of biomedical diagnostic imaging. For many years during this timeframe, F imaging research continued at a slow pace as the various attributes of the technique were explored. However, over the last decade and particularly the last several years, the pace and clinical relevance of F imaging has exploded. In part, this is due to advances in MRI instrumentation, F/H coil designs, and ultrafast pulse sequence development for both preclinical and clinical scanners. These achievements, coupled with interest in the molecular imaging of anatomy and physiology, and combined with a cadre of innovative agents, have brought the concept of F into early clinical evaluation. In this review, we attempt to provide a slice of this rich history of research and development, with a particular focus on liquid perfluorocarbon compound-based agents.
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http://dx.doi.org/10.15302/J-ENG-2015103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841681PMC
December 2015

Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging.

Eur Radiol 2017 Feb 22;27(2):578-588. Epub 2016 Mar 22.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.

Objectives: To investigate whether amide proton transfer (APT) MR imaging can differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) among gliomas without intense contrast enhancement (CE).

Methods: This retrospective study evaluated 34 patients (22 males, 12 females; age 36.0 ± 11.3 years) including 20 with LGGs and 14 with HGGs, all scanned on a 3T MR scanner. Only tumours without intense CE were included. Two neuroradiologists independently performed histogram analyses to measure the 90th-percentile (APT) and mean (APT) of the tumours' APT signals. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were also measured. The parameters were compared between the groups with Student's t-test. Diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis.

Results: The APT (2.80 ± 0.59 % in LGGs, 3.72 ± 0.89 in HGGs, P = 0.001) and APT (1.87 ± 0.49 % in LGGs, 2.70 ± 0.58 in HGGs, P = 0.0001) were significantly larger in the HGGs compared to the LGGs. The ADC and rCBV values were not significantly different between the groups. Both the APT and APT showed medium diagnostic performance in this discrimination.

Conclusions: APT imaging is useful in discriminating HGGs from LGGs among diffuse gliomas without intense CE.

Key Points: • Amide proton transfer (APT) imaging helps in grading non-enhancing gliomas • High-grade gliomas showed higher APT signal than low-grade gliomas • APT imaging showed better diagnostic performance than diffusion- and perfusion-weighted imaging.
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http://dx.doi.org/10.1007/s00330-016-4328-0DOI Listing
February 2017

Amide proton transfer (APT) magnetic resonance imaging of prostate cancer: comparison with Gleason scores.

MAGMA 2016 Aug 10;29(4):671-9. Epub 2016 Mar 10.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.

Objective: To evaluate the utility of amide proton transfer (APT) imaging in estimating the Gleason score (GS) of prostate cancer (Pca).

Materials And Methods: Sixty-six biopsy-proven cancers were categorized into four groups according to the GS: GS-6 (3 + 3); GS-7 (3 + 4/4 + 3); GS-8 (4 + 4) and GS-9 (4 + 5/5 + 4). APT signal intensities (APT SIs) and apparent diffusion coefficient (ADC) values of each GS group were compared by one-way analysis of variance with Tukey's HSD post hoc test.

Results: The mean and standard deviation of the APT SIs (%) and ADC values (×10(-3) mm(2)/s) were as follows: GS-6, 2.48 ± 0.59 and 1.16 ± 0.26; GS-7, 5.17 ± 0.66 and 0.92 ± 0.18; GS-8, 2.56 ± 0.85 and 0.86 ± 0.17; GS-9, 1.96 ± 0.75 and 0.85 ± 0.18, respectively. The APT SI of the GS-7 group was highest, and there were significant differences between the GS-6 and GS-7 groups and the GS-7 and GS-9 groups (p < 0.05). The ADC value of the GS-6 group was significantly higher than each value of the GS-7, GS-8, and GS-9 groups (p < 0.05), but no significant differences were obtained among the GS-7, GS-8, and GS-9 groups.

Conclusion: The mean APT SI in Pca with a GS of 7 was higher than that for the other GS groups.
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http://dx.doi.org/10.1007/s10334-016-0537-4DOI Listing
August 2016

Multiparametric MRI analysis for the evaluation of MR-guided high intensity focused ultrasound tumor treatment.

NMR Biomed 2015 Sep 21;28(9):1125-40. Epub 2015 Jul 21.

Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T1, T2, ADC, amide proton transfer (APT), T1ρ and DCE-MRI measurements, to evaluate MR-guided HIFU treatment of subcutaneous tumors in rats. K-means clustering using all different combinations of the endogenous contrast MRI parameters (feature vectors) was performed to segment the multiparametric data into tissue populations with similar MR parameter values. The optimal feature vector for identification of the extent of non-viable tumor tissue after HIFU treatment was determined by quantitative comparison between clustering-derived and histology-derived non-viable tumor fractions. The highest one-to-one correspondence between these clustering-based and histology-based non-viable tumor fractions was observed for the feature vector {ADC, APT-weighted signal} (R(2) to line of identity (R(2)y=x) = 0.92) and the strongest agreement was seen 3 days after HIFU (R(2)y=x = 0.97). To compare the multiparametric MRI analysis results with conventional HIFU monitoring and evaluation methods, the histology-derived non-viable tumor fractions were also quantitatively compared with non-perfused tumor fractions (derived from the level of contrast enhancement in the DCE-MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240 cumulative equivalent minutes at 43 °C). The correlation between histology-derived non-viable tumor fractions directly after HIFU and the 240 CEM fractions was high, but not significant. The non-perfused fractions overestimated the extent of non-viable tumor tissue directly after HIFU, whereas an underestimation was observed 3 days after HIFU. In conclusion, we have shown that a multiparametric MR analysis, especially based on the ADC and the APT-weighted signal, can potentially be used to determine the extent of non-viable tumor tissue 3 days after HIFU treatment. We expect that this method can be incorporated in the current clinical workflow of MR-HIFU ablation therapies.
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http://dx.doi.org/10.1002/nbm.3350DOI Listing
September 2015

Scan-rescan reproducibility of parallel transmission based amide proton transfer imaging of brain tumors.

J Magn Reson Imaging 2015 Nov 30;42(5):1346-53. Epub 2015 Mar 30.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Purpose: To evaluate the reproducibility of amide proton transfer (APT) imaging of brain tumors using a parallel transmission-based technique.

Materials And Methods: Thirteen patients with brain tumors (four low-grade gliomas, three glioblastoma multiforme, five meningiomas, and one malignant lymphoma) were included in the study. APT imaging was conducted at 3T using a 2-channel parallel transmission scheme with a saturation time of 2 seconds and B1 amplitude of 2 μT. A 2D fast spin-echo sequence with driven-equilibrium refocusing was used for imaging. Z-spectra were obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. A scan-rescan reproducibility test was performed in two sessions on separate days for each patient. The interval between the two sessions was 4.8 ± 3.5 days. Regions-of-interest (ROIs) were placed to include the whole tumor for each case. A mean and 90-percentile value of APT signal for the whole tumor histogram was calculated for each session. The between-session and within-session reproducibility was evaluated using linear regression analysis, intraclass correlation coefficient (ICC), and a Bland-Altman plot.

Results: The mean and 90-percentile values of the APT signal for whole tumor ROI showed excellent agreements between the two sessions, with R(2) of 0.91 and 0.96 in the linear regression analysis and ICC of 0.95 and 0.97, respectively.

Conclusion: Parallel transmission-based APT imaging of brain tumors showed good reproducibility.
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http://dx.doi.org/10.1002/jmri.24895DOI Listing
November 2015

Balanced UTE-SSFP for 19F MR imaging of complex spectra.

Magn Reson Med 2015 Aug 27;74(2):537-43. Epub 2014 Aug 27.

Department of Biomedical Engineering, Washington University in St. Louis, Missouri, USA.

Purpose: A novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout.

Methods: Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2 )6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE.

Results: The proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 μmolPFOB(-1) min(-1/2) (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 μmolPFOB(-1) min(-1/2) ) or Cartesian k-space filling (GRE: 12 μmolPFOB(-1) min(-1/2) ; FSE: 16 μmolPFOB(-1) min(-1/2) ; balanced SSFP: 23 μmolPFOB(-1) min(-1/2) ). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner.

Conclusion: A new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra.
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http://dx.doi.org/10.1002/mrm.25437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483146PMC
August 2015

Angiogenesis and airway reactivity in asthmatic Brown Norway rats.

Angiogenesis 2015 Jan 23;18(1):1-11. Epub 2014 Aug 23.

Department of Medicine, Johns Hopkins University, Baltimore, MD, USA,

Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 μg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvβ3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.
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http://dx.doi.org/10.1007/s10456-014-9441-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281493PMC
January 2015

MR cholangiography demonstrates unsuspected rapid biliary clearance of nanoparticles in rodents: implications for clinical translation.

Nanomedicine 2014 Oct 14;10(7):1385-8. Epub 2014 May 14.

Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.

Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid (<5 min) biliary elimination of gadolinium-perfluorocarbon nanoparticles (approximately 250 nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity. From the clinical editor: Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications of nanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepatic clearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals and humans, raising awareness of important differences between common rodent-based models and larger mammals.
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http://dx.doi.org/10.1016/j.nano.2014.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192078PMC
October 2014

Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades.

Neuro Oncol 2014 Mar 4;16(3):441-8. Epub 2013 Dec 4.

Department of Molecular Imaging and Diagnosis, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan (O.T.); Department of Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan (O.T., T.Y., A.H., K.Y., K.K., H.H.); Philips Research, Hamburg, Germany (J.K.); Philips Electronics Japan, Tokyo, Japan (Y.S.); Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (S.O.S., T.I.); Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (N.H., M.M., K.Y.); Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas (K.S., M.T.).

Background: Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. We prospectively assessed the usefulness of APT imaging in predicting the histological grade of adult diffuse gliomas.

Methods: Thirty-six consecutive patients with histopathologically proven diffuse glioma (48.1 ± 14.7 y old, 16 males and 20 females) were included in the study. APT MRI was conducted on a 3T clinical scanner and was obtained with 2 s saturation at 25 saturation frequency offsets ω = -6 to +6 ppm (step 0.5 ppm). δB0 maps were acquired separately for a point-by-point δB0 correction. APT signal intensity (SI) was defined as magnetization transfer asymmetry at 3.5 ppm: magnetization transfer ratio (MTR)asym = (S[-3.5 ppm] - S[+3.5 ppm])/S0. Regions of interest were carefully placed by 2 neuroradiologists in solid parts within brain tumors. The APT SI was compared with World Health Organization grade, Ki-67 labeling index (LI), and cell density.

Results: The mean APT SI values were 2.1 ± 0.4% in grade II gliomas (n = 8), 3.2 ± 0.9% in grade III gliomas (n = 10), and 4.1 ± 1.0% in grade IV gliomas (n = 18). Significant differences in APT intensity were observed between grades II and III (P < .05) and grades III and IV (P < .05), as well as between grades II and IV (P < .001). There were positive correlations between APT SI and Ki-67 LI (P = .01, R = 0.43) and between APT SI and cell density (P < .05, R = 0.38). The gliomas with microscopic necrosis showed higher APT SI than those without necrosis (P < .001).

Conclusions: APT imaging can predict the histopathological grades of adult diffuse gliomas.
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http://dx.doi.org/10.1093/neuonc/not158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922507PMC
March 2014

Characterization of early neovascular response to acute lung ischemia using simultaneous (19)F/ (1)H MR molecular imaging.

Angiogenesis 2014 Jan 6;17(1):51-60. Epub 2013 Aug 6.

Department of Medicine, Washington University School of Medicine, 660 S. Euclid, Campus Box 8215, St. Louis, MO, 63110, USA,

Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3 days after LPAL, simultaneous (19)F/(1)H MR imaging at 3T revealed a marked (19)F signal in animals 2 h following αvβ3-targeted perfluorocarbon nanoparticles [(19)F signal (normalized to background) = 0.80 ± 0.2] that was greater (p = 0.007) than the non-targeted (0.30 ± 0.04) and the sham-operated (0.07 ± 0.09) control groups. Almost no (19)F signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the (19)F signal (p = 0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.
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http://dx.doi.org/10.1007/s10456-013-9377-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947345PMC
January 2014

Dynamic and simultaneous MR measurement of R1 and R2* changes during respiratory challenges for the assessment of blood and tissue oxygenation.

Magn Reson Med 2013 Jul 24;70(1):136-46. Epub 2012 Aug 24.

Philips Research, Hamburg, Germany.

This work presents a novel method for the rapid and simultaneous measurement of R1 and R2* relaxation rates. It is based on a dynamic short repetition time steady-state spoiled multigradient-echo sequence and baseline R1 and B1 measurements. The accuracy of the approach was evaluated in simulations and a phantom experiment. The sensitivity and specificity of the method were demonstrated in one volunteer and in four patients with intracranial tumors during carbogen inhalation. We utilized (ΔR2*, ΔR1) scatter plots to analyze the multiparametric response amplitude of each voxel within an area of interest. In normal tissue R2* decreased and R1 increased moderately in response to the elevated blood and tissue oxygenation. A strong negative ΔR2* and ΔR1 response was observed in veins and some tumor areas. Moderate positive ΔR2* and ΔR1 response amplitudes were found in fluid-rich tissue as in cerebrospinal fluid, peritumoral edema, and necrotic areas. The multiparametric approach was shown to increase the specificity and sensitivity of oxygen-enhanced MRI compared to measuring ΔR2* or ΔR1 alone. It is thus expected to provide an optimal tool for the identification of tissue areas with low oxygenation, e.g., in tumors with compromised oxygen supply.
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http://dx.doi.org/10.1002/mrm.24458DOI Listing
July 2013

Ytterbium-based PARACEST agent: feasibility of CEST imaging on a clinical MR scanner.

Magn Reson Med Sci 2012 ;11(1):35-41

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Purpose: We investigated the feasibility of performing chemical exchange saturation transfer (CEST) imaging using ytterbium-based paramagnetic CEST (PARACEST) agents on a clinical magnetic resonance (MR) scanner.

Materials And Methods: We prepared solutions of 3 different ytterbium-based PARACEST agents at concentrations of 5, 10, 20, and 50 mM at a pH of 7.4 and at a concentration of 50 mM at pHs of 3.0, 5.0, 7.4, and 9.5. We acquired images with a turbo spin echo technique using a quadrature head coil and a clinical 3.0-tesla MR system in accordance with the safety limits of the specific absorption rate (SAR). We acquired CEST images with presaturation offset frequencies from -5,000 Hz (-39.1 ppm) to 5,000 Hz (39.1 ppm) with an interval of 500 Hz (3.9 ppm) for each condition. We repeated each scan 3 times and then calculated the mean and standard deviations of the magnitude of the CEST effect at different concentrations and pH values for each agent. We used one-way analysis of variance and Tukey's honestly significant difference post hoc test to compare mean values of the magnitude of the CEST effect obtained at different concentrations and pH values. P < 0.05 was considered significant.

Results: PARACEST agents showed a strong CEST effect at their specific presaturation offset frequencies. For each agent, the CEST effect showed significant concentration dependency (P < 0.05), increasing with agent concentration, and significant pH dependency (P < 0.05), with strong effect near physiological pH.

Conclusion: CEST imaging using ytterbium-based PARACEST agents might be feasible on a clinical MR scanner with further modifications, such as adjustments of the presaturation radiofrequency pulse and imaging protocols.
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http://dx.doi.org/10.2463/mrms.11.35DOI Listing
August 2012

Simultaneous dual-nuclei imaging for motion corrected detection and quantification of 19F imaging agents.

Magn Reson Med 2011 Oct 9;66(4):1116-22. Epub 2011 Mar 9.

Philips Technologie GmbH, Innovative Technologies, Research Laboratories, Hamburg, Germany.

Fluorine MRI offers broad potential for specific detection and quantification of molecularly targeted agents in diagnosis and therapy planning or monitoring. Because non-proton MRI applications lack morphological information, accompanying proton images are needed to elucidate the spatial tissue context. Furthermore, low concentrations typical of targeted molecular imaging agents require long examinations for signal averaging during which physiological motion may lead to blurring, underestimation in signal quantification, and erroneous localization of the agent distribution. Novel methods for truly simultaneous acquisition of dual-nuclei MR data are presented that offer efficient and precise anatomical localization of fluorine signals using accurate motion correction based on contemporaneous proton signals. The feasibility of simultaneous dual-nuclei MRI motion correction and corresponding dual-resolution reconstruction, providing nuclei-specific spatial resolution to retrospectively optimize the balance between signal-to-noise ratio and resolution, is shown on a clinical 3 T MR system.
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http://dx.doi.org/10.1002/mrm.22877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202693PMC
October 2011

Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T.

Magn Reson Med 2011 Jan;65(1):202-11

Department of Chemistry IFM and Center for Molecular Imaging, University of Torino, Torino, Italy.

Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition.
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http://dx.doi.org/10.1002/mrm.22608DOI Listing
January 2011

Towards automatic patient positioning and scan planning using continuously moving table MR imaging.

Magn Reson Med 2009 Oct;62(4):1067-72

Philips Research Europe, Hamburg, Germany.

A concept is proposed to simplify patient positioning and scan planning to improve ease of use and workflow in MR. After patient preparation in front of the scanner the operator selects the anatomy of interest by a single push-button action. Subsequently, the patient table is moved automatically into the scanner, while real-time 3D isotropic low-resolution continuously moving table scout scanning is performed using patient-independent MR system settings. With a real-time organ identification process running in parallel and steering the scanner, the target anatomy can be positioned fully automatically in the scanner's sensitive volume. The desired diagnostic examination of the anatomy of interest can be planned and continued immediately using the geometric information derived from the acquired 3D data. The concept was implemented and successfully tested in vivo in 12 healthy volunteers, focusing on the liver as the target anatomy. The positioning accuracy achieved was on the order of several millimeters, which turned out to be sufficient for initial planning purposes. Furthermore, the impact of nonoptimal system settings on the positioning performance, the signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) was investigated. The present work proved the basic concept of the proposed approach as an element of future scan automation.
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http://dx.doi.org/10.1002/mrm.22069DOI Listing
October 2009