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Background: Tendon and bone comprise a critical interrelating unit. Bone loss, including that seen with osteopenia (OPe) or osteoporosis (OPo), may be associated with a reduction in tendon quality, though this remains incompletely investigated. Clinical magnetic resonance imaging (MRI) sequences cannot directly detect signals from tendons because of the very short T2. Clinical MRI may detect high-graded abnormalities by changes in the adjacent structures like bone. However, ultrashort echo time MRI (UTE-MRI) can capture high signals from all tendons. To determine if the long T2 fraction, as measured by a dual-echo UTE-MRI sequence, is a sensitive quantitative technique to the age- and bone-loss-related changes of the lower leg tendons., Methods: This is a cross-sectional study conducted between January 2018 to February 2020 in the lower legs of 14 female patients with OPe [72±6 years old, body mass index (BMI) =25.8±6.2 kg/m 2 ] and 31 female patients with OPo (73±6 years old, BMI=22.0±3.8 kg/m 2 ), as well as 30 female subjects with normal bone (Normal, 35±18 years old, BMI =23.2±4.3 kg/m 2 ), were imaged on a 3T clinical scanner using a dual-echo 3D Cones UTE sequence. We defined the apparent long T2 signal fraction (aFrac-LongT2) of tendons as the ratio between the signal at the second echo time (TE =2.2 ms) to the UTE signal. The average aFrac-LongT2 and the cross-sectional area were calculated for the anterior tibialis tendons (ATTs) and the posterior tibialis tendons (PTTs). The Kruskal-Wallis rank test was used to compare the differences in aFrac-LongT2 and the cross-sectional area of the tendons between the groups., Results: The aFrac-LongT2 of the ATTs and PTTs were significantly higher in the OPo group compared with the Normal group (22.2% and 34.8% in the ATT and PTT, respectively, P<0.01). The cross-sectional area in the ATTs was significantly higher for the OPo group than in the Normal group (Normal/OPo difference was 28.7, P<0.01). Such a difference for PTTs did not reach the significance level. Mean aFrac-LongT2 and cross-sectional area in the OPe group were higher than the Normal group and lower than the OPo group. However, the differences did not show statistical significance, likely due to the higher BMI in the OPe group., Conclusions: Dual-echo UTE-MRI is a rapid quantification technique, and aFrac-LongT2 values showed significant differences in tendons between Normal and OPo patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1341/coif). Jiang Du serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. All authors report that this study was supported by GE Healthcare. GE Healthcare was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions., Method: Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison., Results: The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM., Conclusions: The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1021/coif). J.D. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. G.M.B. is a clinical consultant to Magnetica, Brisbane, Australia. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T 1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T 1 by up to 15 times compared to conventional T 1 -weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T 1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T 2 -weighted spin echo (T 2 -wSE) and/or fluid attenuated inversion recovery (T 2 -FLAIR) images. The small changes in T 1 or T 2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T 1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T 1 maps. There is a nearly linear relationship between signal and T 1 in the middle domain (mD) of the two sequences which includes T 1 s between the nulling T 1 s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T 1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T 1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T 2 -wSE and T 2 -FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T 1 -bipolar filters; to explain their targeting, signal, contrast, boundaries, T 1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-232/coif). JD serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. MNJP is a scientific and technical adviser to Magnetica, Brisbane, Australia. GMB is a clinical consultant to Magnetica, Brisbane, Australia. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: In this study, we investigated the feasibility of quantitative ultrashort echo time (qUTE) magnetic resonance (MR) imaging techniques in the detection and quantification of iron oxide nanoparticle (IONP)-labeled stem cells., Methods: A stem cell phantom containing multiple layers of unlabeled or labeled stem cells with different densities was prepared. The phantom was imaged with quantitative UTE (qUTE) MR techniques [i.e., UTE-T 1 mapping, UTE-T 2 * mapping, and UTE-based quantitative susceptibility mapping (UTE-QSM)] as well as with a clinical T 2 mapping sequence on a 3T clinical MR system. For T 1 mapping, a variable flip angle (VFA) method based on actual flip angle imaging (AFI) technique was utilized. For T 2 * mapping and UTE-QSM, multiple images with variable, interleaved echo times including UTE images and gradient recalled echo (GRE) images were used. For UTE-QSM, the phase information from the multi-echo images was utilized and processed using a QSM framework based on the morphology-enabled dipole inversion (MEDI) algorithm. The qUTE techniques were also evaluated in an ex vivo experiment with a mouse injected with IONP-labeled stem cells., Results: In the phantom experiment, the parameters estimated with qUTE techniques showed high linearity with respect to the density of IONP-labeled stem cells (R 2 >0.99), while the clinical T 2 parameter showed impaired linearity (R 2 =0.87). In the ex vivo mouse experiment, UTE-T 2 * mapping and UTE-QSM showed feasibility in the detection of injected stem cells with high contrast, whereas UTE-T 1 and UTE-T 2 * showed limited detection. Overall, UTE-QSM demonstrated the best contrast of all, with other methods being subjected more to a confounding factor due to different magnetic susceptibilities of various types of neighboring tissues, which creates inhomogeneous contrast that behaves similar to IONP., Conclusions: In this study, we evaluated the feasibility of a series of qUTE imaging techniques as well as conventional T 2 mapping for the detection of IONP-labeled stem cells in vitro and ex vivo . UTE-QSM performed superior amongst other qUTE techniques as well as conventional T 2 mapping in detecting stem cells with high contrast., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-654/coif). JA and MT are employees of VisiCELL Medical Inc. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

This paper updates and extends three previous papers on tissue property filters (TP-filters), Multiplied, Added, Divided and/or Subtracted Inversion Recovery (MASTIR) pulse sequences and synergistic contrast MRI (scMRI). It does this by firstly adding the central contrast theorem (CCT) to TP-filters, secondly including division with MASTIR sequences to make them Multiplied, Added, Subtracted and/or Divided IR (MASDIR) sequences, and thirdly incorporating division into the image processing needed for scMR to increase synergistic T 1 contrast. These updated concepts are then used to explain and improve contrast at tissue boundaries, as well as to develop imaging regimes to detect and monitor small changes to the brain over time and quantify T 1 . The CCT is in two parts: the first part states that contrast produced by each TP is the product of the change in TP multiplied by the TP sequence weighting which is the first partial derivative of the TP-filter. The second part states that the overall fractional contrast is the algebraic sum of the fractional contrasts produced by each of the TPs. Subtraction of two IR sequences alone about doubles contrast relative to a conventional single IR sequence. Division of this subtraction can amplify contrast 5-15 times compared with conventional IR sequences. Dividing sequences can be problematic in areas where the signal is zero but this is avoided by dividing the difference in signal of two magnitude reconstructed IR sequences by the sum of their signals. The basis for the production of high contrast, high spatial resolution boundaries at white-gray matter junctions, between cerebral cortex and cerebrospinal fluid (CSF) and at other sites with subtracted IR (SIR) and divided subtracted IR (dSIR) sequences is explained and examples are shown. A key concept is the tissue fraction f, which is the proportion of a tissue in a mixture of two tissues within a voxel. Contrast at boundaries is a function of the partial derivative of the TP-filter, the partial derivative of the relevant TP with respect to f, and the partial derivative of f with respect to distance, x. Location of tissue boundaries is important for segmentation and is helpful in determining if inversion times have been chosen correctly. In small change regimes, the high sensitivity to small changes in T 1 provided by dSIR images, together with the high definition boundaries, afford mechanisms for detecting small changes due to contrast agents, disease, perfusion and other causes. 3D isotropic rigid body registration provides a technique for following these changes over time in serial studies. Images showing high lesion contrast, high definition tissue and fluid boundaries, and the detection of small changes are included. T1 maps can be created by linearly scaling dSIR images., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-394/coif). JD serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. GMB is a consultant to Magnetica. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)