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Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1‐13C]pyruvate MRS and [18F]FDG‐PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells. [1‐13C]pyruvate was hyperpolarized by dissolution dynamic nuclear polarization (dDNP) and [1‐13C]pyruvate to lactate conversion was followed by 13C MRS. Subsequently [18F]FDG uptake was investigated by static and dynamic PET measurements. Standard uptake values (SUVs) for [18F]FDG were significantly higher for xenografts of PC3 compared with those of LNCaP. However, we did not observe a difference in the average apparent rate constant kpl of 13C label exchange from pyruvate to lactate between the tumor variants. A significant negative correlation was found between SUVs from [18F]FDG PET measurements and kpl values for the xenografts of both tumor types. The kpl rate constant may be influenced by various factors, and studies with a range of prostate cancer cells in suspension suggest that LDH inhibition by pyruvate may be one of these. Our results indicate that glucose and pyruvate metabolism in the prostate cancer cell models differs from that in other tumor models and that [18F]FDG‐PET can serve as a valuable complementary tool in dDNP studies of aggressive prostate cancer with [1‐13C]pyruvate. [ABSTRACT FROM AUTHOR]

1H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high‐field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T1 and T2* values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T2* relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T2* values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T2 values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T1 values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal‐to‐noise‐ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC‐filled lesions showed less homogeneous structures, a lower T1 value and T2* separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed. [ABSTRACT FROM AUTHOR]

Boiling histotripsy (BH) is a new high intensity focused ultrasound (HIFU) ablation technique to mechanically fragmentize soft tissue into submicrometer fragments. So far, ultrasound has been used for BH treatment guidance and evaluation. The in vivo histopathological effects of this treatment are largely unknown. Here, we report on an MR guided BH method to treat subcutaneous tumors in a mouse model. The treatment effects of BH were evaluated one hour and four days later with MRI and histopathology, and compared with the effects of thermal HIFU (T-HIFU). The lesions caused by BH were easily detected with T2w imaging as a hyper-intense signal area with a hypo-intense rim. Histopathological evaluation showed that the targeted tissue was completely disintegrated and that a narrow transition zone (<200 µm) containing many apoptotic cells was present between disintegrated and vital tumor tissue. A high level of agreement was found between T2w imaging and H&E stained sections, making T2w imaging a suitable method for treatment evaluation during or directly after BH. After T-HIFU, contrast enhanced imaging was required for adequate detection of the ablation zone. On histopathology, an ablation zone with concentric layers was seen after T-HIFU. In line with histopathology, contrast enhanced MRI revealed that after BH or T-HIFU perfusion within the lesion was absent, while after BH in the transition zone some micro-hemorrhaging appeared. Four days after BH, the transition zone with apoptotic cells was histologically no longer detectable, corresponding to the absence of a hypo-intense rim around the lesion in T2w images. This study demonstrates the first results of in vivo BH on mouse tumor using MRI for treatment guidance and evaluation and opens the way for more detailed investigation of the in vivo effects of BH. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We developed a new dedicated measurement protocol for dynamic 31P MRS analysis in contracting calf muscles of the mouse, using minimally invasive assessment of the contractile force combined with the acquisition of spectroscopic data gated to muscle contraction and determination of phosphocreatine (PCr) recovery rate and ATP contractile cost. This protocol was applied in a comparative study of six wild type (WT) mice and six mice deficient in cytosolic creatine kinase and adenylate kinase isoform 1 (MAK−/− mice) using 70 repeated tetanic contractions at two contractions per minute. Force levels during single contractions, and metabolite levels and tissue pH during resting conditions were similar in muscles of MAK−/− and WT mice. Strikingly, muscle relaxation after contraction was significantly delayed in MAK−/− mice, but during repeated contractions, the decrease in the force was similar in both mouse types. Gated data acquisition showed a negligible PCr breakdown in MAK−/− immediately after contraction, without a concomitant decrease in ATP or tissue pH. This protocol enabled the determination of rapid PCr changes that would otherwise go unnoticed due to intrinsic low signal-to-noise ratio (SNR) in mouse skeletal muscles combined with an assessment of the PCr recovery rate. Our results suggest that MAK−/− mice use alternative energy sources to maintain force during repeated contractions when PCr breakdown is reduced. Furthermore, the absence of large increases in adenosine diphosphate (ADP) or differences in force compared to WT mice in our low-intensity protocol indicate that creatine kinase (CK) and adenylate kinase (AK) are especially important in facilitating energy metabolism during very high energy demands. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In the surgical treatment of vulvar squamous‐cell carcinoma (VSCC), tumor‐free margins of 8 mm or more are considered adequate. However, limited perioperative information on the tumor‐free margins other than the surgeon's own estimation is available. The purpose of this study was therefore to investigate the feasibility of ex vivo MRI in localizing VSCC and to assess the surgical tumor‐free margins in fresh radical local excision (RLE) specimens to guide the surgeon during resections. Nine patients with biopsy‐proven VSCC scheduled for RLE were prospectively included. Intact fresh specimens were scanned using a 7 T preclinical MR‐scanner. Whole mount H&E‐stained slides were obtained every 3 mm and correlated with ex vivo MRI. A pathologist annotated VSCC and minimal tumor‐free margins (3 o'clock, 9 o'clock, basal) on the digitalized histological slides. An observer with knowledge of histology (the non‐blinded annotation) and a radiologist blinded to histology (the blinded annotation) separately performed annotation of the same features on ex vivo MRI. Linear correlation and agreement of the ex vivo MRI measurements with histology were assessed. Diagnostic performance for VSCC localization and identification of margins less than 8 mm was expressed as positive and negative predictive values (PPV, NPV). In 153 matched ex vivo MRI slices, the observer correctly identified 79/91 margins as less than 8 mm (PPV 87%) and 110/124 margins as 8 mm or greater (NPV 89%). The radiologist correctly annotated absence of VSCC in 73/81 (NPV 90%) and presence in 65/72 (PPV 90%) slices. Sixty‐four of 90 margins were correctly identified as less than 8 mm (PPV 71%) and 83/102 margins as 8 mm or greater (NPV 81%). Both non‐blinded and blinded annotations were linearly correlated and demonstrated good agreement with histology. Accurate localization of VSCC and measurements of the surgical tumor‐free margins in fresh RLE specimens using ex vivo MRI seems feasible. High diagnostic performance in VSCC localization and identification of margins less than 8 mm suggest ex vivo MRI to be clinically applicable. This study assessed the feasibility of 7 T ex vivo MRI in localizing vulvar squamous‐cell carcinoma (VSCC) and assessing tumor‐free margins in fresh radical local excision specimens to guide the surgeon. Annotations of VSCC and tumor‐free margins on ex vivo MRI were directly compared with histology. The results demonstrated high diagnostic performance in VSCC localization and identification of margins less than 8 mm as well as high correlation and agreement between ex vivo MRI and histology which suggest clinical applicability. [ABSTRACT FROM AUTHOR]

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1- 13 C]pyruvate MRS and [ 18 F]FDG-PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells. [1- 13 C]pyruvate was hyperpolarized by dissolution dynamic nuclear polarization (dDNP) and [1- 13 C]pyruvate to lactate conversion was followed by 13 C MRS. Subsequently [ 18 F]FDG uptake was investigated by static and dynamic PET measurements. Standard uptake values (SUVs) for [ 18 F]FDG were significantly higher for xenografts of PC3 compared with those of LNCaP. However, we did not observe a difference in the average apparent rate constant k pl of 13 C label exchange from pyruvate to lactate between the tumor variants. A significant negative correlation was found between SUVs from [ 18 F]FDG PET measurements and k pl values for the xenografts of both tumor types. The k pl rate constant may be influenced by various factors, and studies with a range of prostate cancer cells in suspension suggest that LDH inhibition by pyruvate may be one of these. Our results indicate that glucose and pyruvate metabolism in the prostate cancer cell models differs from that in other tumor models and that [ 18 F]FDG-PET can serve as a valuable complementary tool in dDNP studies of aggressive prostate cancer with [1- 13 C]pyruvate., (© 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

1 H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T 1 and T 2 * values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T 2 * relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T 2 * values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T 2 values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T 1 values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal-to-noise-ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC-filled lesions showed less homogeneous structures, a lower T 1 value and T 2 * separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed., (Copyright © 2017 John Wiley & Sons, Ltd.)

We developed a new dedicated measurement protocol for dynamic (31)P MRS analysis in contracting calf muscles of the mouse, using minimally invasive assessment of the contractile force combined with the acquisition of spectroscopic data gated to muscle contraction and determination of phosphocreatine (PCr) recovery rate and ATP contractile cost. This protocol was applied in a comparative study of six wild type (WT) mice and six mice deficient in cytosolic creatine kinase and adenylate kinase isoform 1 (MAK(-/-) mice) using 70 repeated tetanic contractions at two contractions per minute. Force levels during single contractions, and metabolite levels and tissue pH during resting conditions were similar in muscles of MAK(-/-) and WT mice. Strikingly, muscle relaxation after contraction was significantly delayed in MAK(-/-) mice, but during repeated contractions, the decrease in the force was similar in both mouse types. Gated data acquisition showed a negligible PCr breakdown in MAK(-/-) immediately after contraction, without a concomitant decrease in ATP or tissue pH. This protocol enabled the determination of rapid PCr changes that would otherwise go unnoticed due to intrinsic low signal-to-noise ratio (SNR) in mouse skeletal muscles combined with an assessment of the PCr recovery rate. Our results suggest that MAK(-/-) mice use alternative energy sources to maintain force during repeated contractions when PCr breakdown is reduced. Furthermore, the absence of large increases in adenosine diphosphate (ADP) or differences in force compared to WT mice in our low-intensity protocol indicate that creatine kinase (CK) and adenylate kinase (AK) are especially important in facilitating energy metabolism during very high energy demands., (2009 John Wiley & Sons, Ltd.)