Gradient-echo-train-based sub-millisecond periodic event encoded dynamic imaging with random (k, t)-space undersampling: k-t get-SPEEDI.

PURPOSE: The gradient-echo-train-based Sub-millisecond Periodic Event Encoded Dynamic Imaging (get-SPEEDI) technique provides ultrahigh temporal resolutions (∼0.6 ms) for detecting rapid physiological activities, but its practical adoption can be hampered by long scan times. This study aimed at developing a more efficient variant of get-SPEEDI for reducing the scan time without degrading temporal resolution or image quality. METHODS: The proposed pulse sequence, named k-t get-SPEEDI, accelerated get-SPEEDI acquisition by undersampling the k-space phase-encoding lines semi-randomly. At each time frame, k-space was fully sampled in the central region whereas randomly undersampled in the outer regions. A time-series of images was reconstructed using an algorithm based on the joint partial separability and sparsity constraints. To demonstrate the performance of k-t get-SPEEDI, images of human aortic valve opening and closing were acquired with 0.6-ms temporal resolution and compared with those from conventional get-SPEEDI. RESULTS: k-t get-SPEEDI achieved a 2-fold scan time reduction over the conventional get-SPEEDI (from ∼6 to ∼3 min), while achieving comparable SNRs and contrast-to-noise ratio (CNRs) for visualizing the dynamic process of aortic valve: SNR/CNR ≈$$ \approx $$ 70/38 vs. 73/39 in the k-t and conventional get-SPEEDI scans, respectively. The time courses of aortic valve area also matched well between these two sequences with a correlation coefficient of 0.86. CONCLUSIONS: The k-t get-SPEEDI pulse sequence was able to half the scan time without compromising the image quality and ultrahigh temporal resolution. Additional scan time reduction may also be possible, facilitating in vivo adoptions of SPEEDI techniques.

Physical activity in elderly kidney transplant patients with multiple renal arteries.

BACKGROUND: Kidney transplantation (KT) is the gold standard for treatment of patients with end-stage-renal disease. To expand the donor reserve, it is necessary to use marginal/suboptimal kidneys. METHODS: We retrospectively evaluated the short/long-term outcome of 34 KT elderly patients who received allografts with vascular abnormalities (MRA group), in comparison with 34 KT patients who received a kidney with a single renal artery (SRA group) pair-matched by age, length of time on dialysis, comorbidity and donor age. RESULTS: All participants completed the International Physical Activity Questionnaire at KT, and then 4, 8, and 12 weeks after transplantation. Our data indicate that kidney with vascular anatomical variants may be successfully transplanted, since the overall rate of surgical complications was 20.6% in the SRA group and 17.6% in the MRA group and that the 5-year survival rate after KT was 100% in both groups. CONCLUSIONS: The data also underlined that individualized physical activity programs induced similar excellent results in both groups, improving physical capacities, arterial pressure, lipid metabolism, insulin sensitivity, quality of life and physical and mental status.

Early detection of increased marrow adiposity with age in rats using Z-spectral MRI at ultra-high field (7 T).

BACKGROUND: Nowadays, the drive towards high-field MRI is fueled by the pursuit of higher signal-to-noise ratio, spatial resolution, and imaging speed. However, high field strength is associated with field inhomogeneity, acceleration of T2 * decay, and increased chemical shift, which may pose challenges to conventional MRI for fat quantification in complex tissues such as bone marrow. With proton MRI spectroscopy (1 H-MRS), on the other hand, it is difficult to produce high resolution. As a novel alternative fat quantification method, high-resolution Z-spectral MRI (ZS-MRI) can achieve fat quantification by acquiring direct saturated images of both fat and water under the same TE , which may be less affected by T2 * decay and field inhomogeneity. PURPOSE: To demonstrate ZS-MRI for marrow adipose tissue (MAT) quantification in rat's lumbar spine and the early detection of MAT changes with age. METHODS: The accuracy of ZS-MRI for fat quantification at ultra-high-field MRI (7 T) was verified with MRS and conventional Dixon MRI in water-oil mixed phantoms with varying fat fraction (FF). Dixon MRI data were processed with iterative decomposition of water and fat with echo asymmetry and least-squares estimation. ZS-MRI was then used to longitudinally monitor the adiposity in the lumbar spine of young healthy rats at 13, 17, and 21 weeks to detect the early changes of FF with age in MAT. Hematoxylin-eosin staining of lumbar spines from separated rat groups was performed for verification. RESULTS: In ex vivo phantom experiments, both Dixon MRI and ZS-MRI were well correlated with 1 H-MRS for the quantification of FF at 7 T (R > 0.99). Compared with Dixon MRI, ZS-MRI showed reduced image artifacts due to field inhomogeneity and presented better agreement with 1 H-MRS for the early detection of increased MAT due to age at 7 T (ZS-MRI R = 0.78 versus Dixon MRI R = 0.34). The increased MAT FF due to age was confirmed by histology. CONCLUSION: ZS-MRI proves itself as an alternative fat quantification method for bone marrow in rats at 7 T.

Phase-independent thermometry by Z-spectrum MR imaging.

PURPOSE: Z-spectrum imaging, defined as the consecutive collection of images after saturating over a range of frequency offsets, has been recently proposed as a method to measure the fat-water fraction by the simultaneous detection of fat and water resonances. By incorporating a binomial pulse irradiated at each offset before the readout, the spectral selectivity of the sequence can be further amplified, making it possible to monitor the subtle proton resonance frequency shift that follows a change in temperature. METHODS: We tested the hypothesis in aqueous and cream phantoms and in healthy mice, all under thermal challenge. The binomial module consisted of 2 sinc-shaped pulses of opposite phase separated by a delay. Such a delay served to spread out off-resonance spins, with the resulting excitation profile being a periodic function of the delay and the chemical shift. RESULTS: During heating experiments, the water resonance shifted downfield, and by fitting the curve to a sine function it was possible to quantify the change in temperature. Results from Z-spectrum imaging correlated linearly with data from conventional MRI techniques like T1 mapping and phase differences from spoiled GRE. CONCLUSION: Because the measurement is performed solely on magnitude images, the technique is independent of phase artifacts and is therefore applicable in mixed tissues (e.g., fat). We showed that Z-spectrum imaging can deliver reliable temperature change measurement in both muscular and fatty tissues.

Combination of natural killer cell-based immunotherapy and irreversible electroporation for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the most lethal cancer types despite great advancement in overall survival of the patients over the last decades. Surgical resection or partial hepatectomy has been approved as the curative treatment for early-stage HCC patients however only up to 30% of them are eligible for the procedures. Natural killer (NK) cells are cytotoxic lymphocytes recognized for killing virally infected cells and improving immune functions for defending the body against malignant cells. Although autologous NK cells failed to demonstrate significant clinical benefit, transfer of allogeneic adoptive NK cells arises as a promising approach for the treatment of solid tumors. The immunosuppressive tumor microenvironment and inadequate homing efficiency of NK cells to tumors can inhibit adoptive transfer immunotherapy (ATI) efficacy. However, potential of the NK cells is challenged by the transfection efficiency. The local ablation techniques that employ thermal or chemical energy have been investigated for the destruction of solid tumors for three decades and demonstrated promising benefits for individuals not eligible for surgical resection or partial hepatectomy. Irreversible electroporation (IRE) is one of the most recent minimally invasive ablation methods that destruct the cell within the targeted region through non-thermal energy. IRE destroys the tumor cell membrane by delivering high-frequency electrical energy in short pulses and overcomes tumor immunosuppression. The previous studies demonstrated that IRE can induce immune changes which can facilitate activation of specific immune responses and improve transfection efficiency. In this review paper, we have discussed the mechanism of NK cell immunotherapy and IRE ablation methods for the treatment of HCC patients and the combinatorial benefits of NK cell immunotherapy and IRE ablation.

Combination of NK-based immunotherapy and sorafenib against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver, which is considered the fourth leading cause of cancer-related death in the United States. Liver transplant and surgical resection are curative treatments for HCC, but only 10-15% of HCC patients are eligible candidates. The FDA-approved sorafenib is a multi-kinase inhibitor systemic therapy for advanced HCC that extends the overall survival by over 3 months when compared with placebo. Adoptive transfer of Natural Killer (NK) cells holds great promise for clinical cancer treatment. However, only limited clinical benefit has been achieved in cancer patients. Therefore, there is currently considerable interest in development of the combination of sorafenib and NK cells for the treatment of HCC patients. However, the mechanism of how sorafenib affects the function of NK cells remains to be comprehensively clarified. In this paper, we will discuss NK cell-based immunotherapies that are currently under preclinical and clinical investigation and its potential combination with sorafenib for improving the survival of HCC patients.

Characterization of microenvironmental changes in the intervertebral discs of patients with chronic low back pain using multiparametric MRI contrasts extracted from Z-spectrum.

PURPOSE: Z-spectral MRI data were analyzed to produce multiparametric metabolic and microenvironmental contrasts for identifying intervertebral discs with/without pain symptom and sore pain. METHODS: Z-spectra data were collected from the lumbar discs of 26 patients with non-specific chronic low bck pain (CLBP) and 21 asymptomatic controls (AC) with a chemical exchange saturation transfer (CEST). Data were fitted to quantify the CEST effects from glycosaminoglycan, amide proton transfer (APT), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer contrast effects, and the direct saturation of water. Multiparametric maps were computed from the fitted peak amplitudes, and the average values were calculated from all five lumber discs. Those parameters were compared between the CLBP and AC groups and between the subgroups with and without (Nsore) sore pain. RESULTS: The discs in symptomatic patients have lower water content, collagen-bound water and collagen than the discs in AC (P < 0.05). Additionally, Z-sepctral MRI indicated that the discs in the sore subgroup had less water, collagen-bound water and collagen, and likely lower pH compared to the Nsore subgroup (P < 0.05). Lower pH as measured with reduced APT and NOE effects may be an important pathological factor causing sore pain of the back. CONCLUSION: Z-spectral MRI with its multiparametric metabolic and microenvironmental contrasts has been demonstrated to identify discs with and without pain symptom or sore pain, providing more important information of CLBP.

Gastroenterological complications in kidney transplant patients.

Kidney transplantation is the surgical operation by which one of the two original kidneys is replaced with another healthy one donated by a compatible individual. In most cases, donors are recently deceased. There is the possibility of withdrawing a kidney from a consenting living subject. Usually, living donors are direct family members, but they could be volunteers completely unrelated to the recipient. A much-feared complication in case of kidney transplantation is the appearance of infections. These tend to arise due to immune-suppressor drugs administered as anti-rejection therapy. In this review, we describe the gastrointestinal complications that can occur in subjects undergoing renal transplantation associated with secondary pathogenic microorganisms or due to mechanical injury during surgery or to metabolic or organic toxicity correlated to anti-rejection therapy. Some of these complications may compromise the quality of life or pose a significant risk of mortality; fortunately, many of them can be prevented and treated without the stopping the immunosuppression, thus avoiding the patient being exposed to the risk of rejection episodes.

COVID-19 and Living Donor Kidney Transplantation in Naples during the Pandemic.

INTRODUCTION: SARS-CoV-2 is a virus that causes a potentially deadly syndrome that affects especially the respiratory tract. Kidney-transplanted patients are immunosuppressed and more susceptible to viral infections. We have examined our transplantation activity to explore the future role of kidney transplantation from deceased and living donors in COVID-19 era. Patients and Methods. The activity of our transplant center of Naples (one of the two transplant centers in Campania, South Italy) continued during the COVID-19 pandemic. We have analysed the kidney transplants carried out between March 9 and June 9, 2020, comparing these data with the numbers of procedures performed in the two previous years. Moreover, we have considered the possibility of performing living donor transplants during a worldwide pandemic. RESULTS: From March 9, 2020, when the Italian lockdown begun, till June 9, 2020, five kidney transplants have been performed at our transplant center in Naples, all from deceased donors. The donors and the recipients have been screened for COVID-19 infection, and the patients, all asymptomatic, followed strict preventive measures and were fully informed about the risks of surgery and immunosuppression during a pandemic. All the transplanted patients remained COVID negative during the follow-up. The number of transplants performed has been constant compared to the same months of 2018 and 2019. In agreement with the patients, we decided to postpone living donor transplants to a period of greater control of the SARS-CoV-2 spread in Italy. CONCLUSION: Deceased donor kidney transplantation should continue, especially in a region with moderate risk, like Campania, with a more careful selection of donors and recipients, preferring standard donors and recipients without severe comorbidities. Living donor transplantation program, instead, should be postponed to a period of greater control of the SARS-CoV-2 spread, as it is an elective surgery and its delay does not determine additional risks for patients.

Relation Between Wound Complication and Lymphocele After Kidney Transplantation: A Monocentric Study.

INTRODUCTION: Wound complication frequently arises after kidney transplantation and its risk factors are well known. In a previous paper we analyzed these factors, and in this new retrospective study we evaluate the influence of lymphocele in the development of wound complications. PATIENTS AND METHODS: From January 2000 to December 2018, 731 consecutive kidney transplants have been performed in our center. We have analyzed the incidence of wound complication and lymphocele and their risk factors. RESULTS: Out of 731 kidney transplants, we have observed wound complications in 115 patients (15.7%) and lymphocele in 158 patients (21.7%). Of these, 70 patients developed both complications (9.5%), but 6 patients have been excluded because they were in therapy with mammalian target of rapamycin inhibitors. Twenty-nine patients (45.3%) presented a first level and 35 patients (54.7%) showed second level wound complications. Lymphocele was the only present factor in just 3 cases (4.6%). The other patients showed diabetes in 28 cases (43.7%), overweight/obesity in 38 (59.3%), delayed graft function in 17 (26.5%), and 60 years or more in 38 (57.8%). The association has been found in 30 out 64 patients treated with tacrolimus (46.8%) and in 34 with cyclosporine (53.1%); 40 patients did not receive muscular layer's reconstruction (62.5%). CONCLUSION: Our experience shows that lymphocele alone is not a predisposing factor for wound dehiscence after kidney transplantation, and they often coexist because they share the same risk factors, the most important being obesity, diabetes and delayed graft function, older age, and surgical techniques. No relation has been observed with calcineurin inhibitor therapy.

Characterization of brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients by Z-Spectral Imaging (ZSI).

PURPOSE: To characterize brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients in comparison to healthy subjects using Z-spectral imaging (ZSI). METHOD: ZSI data were collected on 19 normal control females (NCF), 17 males (NCM), and 13 PCOS patients. By fitting to multiple Lorentzian functions, ZSI provides fat-water fraction (FWF) of tissue in the supraclavicular area that can be used to differentiate between white adipose tissue (WAT), BAT, and muscle. The fraction of BAT over the total fat depot (BATf) and the average FWF in BAT or FWF(BAT) were then computed, reflecting relative BAT mass and BAT metabolism respectively. The parameters were compared among the three groups, and the correlations to Body Mass Index (BMI) were also quantified. RESULTS: There was an inverse correlation between BATf and BMI in normal subjects. The BATf of the PCOS group was significantly smaller than the NCF (P < 0.001). On the other hand, FWF(BAT) correlated linearly with BMI in healthy subjects. The PCOS group had higher FWF(BAT) than the NCF group (P < 0.001). CONCLUSIONS: Normal subjects with higher BMI show less BATf and have increased FWF(BAT), indicating relatively higher level of metabolic passive WAT depot and relatively reduced metabolism in their BAT depots. PCOS patients have the least BATf and the highest FWF(BAT), suggesting decreased BAT mass and function in PCOS. Novel imaging technique with ZSI for the characterization of BAT mass and function in PCOS may help to monitor treatment responses of PCOS therapies.

In vivo quantification of proton exchange rate in healthy human brains with omega plot.

BACKGROUND: To implement omega plot method for in vivo mapping of proton exchange rates in human brain by taking into account the water direct saturation (DS) effect and multiple saturation transfer exchanging species in vivo. METHODS: Four Z-spectra were collected with chemical exchange saturation transfer (CEST) saturation power =1, 2, 3 & 4 µT. Water DS was estimated by fitting the Z-spectrum to a linear combination of multiple Lorentzian components and its contribution to the signal was subsequently removed. Exchange rate maps were derived by the omega plot, consisting of fitting the inverse of the signal intensity, Mz /(M 0-Mz ), as a function of 1/(γB1)2. RESULTS: The exchange rate values quantified with the DS removed omega plot were significantly higher in the GM region than in the WM region (616±29 vs. 575±20 s-1, P<0.001). Phantom studies confirmed that the exchange rates from DS-removed plots varied linearly with pH (R2=0.998) for the pH range of 6.2 to 7.4, whereas exchange rates from conventional omega plots failed to show such linearity in the entire physiological pH range. CONCLUSIONS: The calculated exchange rate with DS-corrected omega plot is a weighted average for all saturation transfer exchanging proton species which contribute to Z-spectral signal. The healthy brain exchange rate map provided by DS-removed omega plots may serve as a baseline for detecting any pathological changes.

Characterization of the microstructure of the intervertebral disc in patients with chronic low back pain by diffusion kurtosis imaging.

PURPOSE: Multivariate analysis of T2-weighted signal, diffusion ADC, and DKI parameters and tractography were used to differentiate chronic non-specific low back pain (CLBP) patients and asymptomatic controls (AC). METHODS: A total of 30 patients with CLBP and 23 AC underwent diffusion kurtosis imaging (DKI) of lumbar spine with a 3T MRI scanner to get the ADC values and seven parameters of DKI in the nucleus pulposus (NP) of the intervertebral disc. The tractography and the tract-related parameters as other parameters were also generated to indicate the intactness of annulus fibrosus (AF). T2-grades of the discs were also quantified based on an eight-grade degeneration grading system. ADC and T2-grades were compared with DKI parameters for the differentiation of CLBP and AC groups. RESULTS: There was no difference in the T2 grades, ADC value, and multiple parameters in DKI of NP between CLBP and AC groups (P > 0.05). The average FA values in NP in AC group were found significantly higher than in the CLBP group (P < 0.05). The scores for the intactness of AF of the intervertebral discs were significantly different in CLBP and AC groups, with 90% of sensitivity and 70% specificity (P < 0.05). Additionally, there were significantly differences in the length and volume values of the AF in CLBP and AC groups (P < 0.05). CONCLUSION: DKI is a good noninvasive method, and it might help to differentiate CLBP from AC. Particularly, the continuation of DKI tractography reflects the presence of annulus fibrosus fissures, an important character in the generation of the low back pain. These slides can be retrieved under Electronic Supplementary Material.

Diffusion kurtosis imaging provides quantitative assessment of the microstructure changes of disc degeneration: an in vivo experimental study.

OBJECTIVE: Our aim was to assess the microstructural changes of intervertebral disc degeneration induced by annulus needle puncture in rats by diffusion kurtosis imaging (DKI). METHODS: Eighteen rats (36 discs) were punctured percutaneously at the intervertebral disc between C6/7, C7/8 (C-coccygeal vertebrae) with a 21-gauge needle. The rats were divided into six groups according to the time after the puncture: 3 h, 48 h, 3 days, 7 days, 10 days and 14 days. There were six discs in three rats in the control group. The rats' tail was imaged at 3T MRI with T2-weighted and diffusion-weighted and diffusion kurtosis imaging (DWI)/DKI sequences. The discs were categorized using a five-grade degeneration system based on the T2 images. The height of the discs and the parameters in DWI/DKI were measured and compared between the different time points. The histological images were also obtained from the discs. RESULTS: The histological study revealed that the discs in the rat of the punctured groups were degenerated. The T2 grades of different groups presented an increasing trend from 7 to 10 days after puncture (R2 = 0.9424, P < 0.001), while the DWI/DKI parameters changes were consistent with the histological changes at the different time points and showed significant differences between the different groups (P < 0.05). CONCLUSIONS: DKI provides quantitative assessment of the microstructure changes of disc degeneration, and it is a non-invasive method. The DKI multi-parameter analysis is sensitive to discs changes caused by puncture. These slides can be retrieved under Electronic Supplementary Material.

Improving the detection specificity of endogenous MRI for reactive oxygen species (ROS).

BACKGROUND: The detection of tissue reactive oxygen species (ROS) using endogenous MRI methods has great potential applications in research and the clinic. We recently demonstrated that ROS produce a significant T1 -shortening effect. However, T1 or T1 -weighted contrast is not specific, as there are many other factors that alter tissue T1 . PURPOSE: To investigate whether the presence of ROS alters tissue environmental conditions such as the proton exchange rate (K ex ) to improve the detection specificity of endogenous ROS MRI. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: The ROS-producing phantoms consisted of fresh egg white treated with H2 O2 and healthy mice injected with pro-oxidative rotenone. FIELD STRENGTH/SEQUENCE: T1 mapping was performed based on fast spin-echo sequence and K ex was evaluated using chemical exchange saturation transfer (CEST) MRI with varied saturation power (QUESP) on a 9.4 T animal scanner. ASSESSMENT: Phantom experiments were conducted to evaluate the overall K ex of CEST-expressing metabolites in fresh egg white treated with H2 O2 of various concentrations (0, 0.025, 0.05, 0.1, and 0.25 v/v%). The egg white phantom continuously produced ROS for more than 3 hours. Various experiments were performed to rule out potential contributing factors to the observed K ex changes. In addition, in vivo MRI study was conducted with a well-established rotenone-exposed mouse model. STATISTICAL TESTS: Student's t-test. RESULTS: Egg white phantoms treated with H2 O2 of various concentrations showed a 26-85% increase in K ex compared with controls. In addition, the K ex of egg white is negligibly affected by other potential confounding factors, including paramagnetic contrast agents (<11%), oxygen (2.3%), and iron oxidation (<10%). Changes in temperature (<1°C) and pH (ΔpH <0.1) in H2 O2 -treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T1 relaxation time (6%) and increased K ex (9%) in rotenone-treated mice. DATA CONCLUSION: We demonstrate that the specificity of endogenous ROS MRI can be improved with the aid of proton exchange rate mapping. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.

Non-invasive Imaging Methods for Brown Adipose Tissue Detection and Function Evaluation.

Brown Adipose Tissue (BAT) has a major role in thermoregulation, producing heat by non-shivering thermogenesis. Primarily found in animals and human infants, the presence of significant brown adipose tissue was identified only recently, and its metabolic role in adults was reconsidered. BAT is believed to have an important role in many metabolic diseases, such as obesity and diabetes, and also to be associated with cancer cachexia. Therefore, it is currently a topic of great interest in the research community, and many groups are investigating the mechanisms underlying BAT metabolism in normal and pathological conditions. However, well established non-invasive methods for assessing BAT distribution and function are still lacking. The purpose of this review is to summarize the current state of the art of these methods, with a particular focus on PET, CT and MRI.

Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.

PURPOSE: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes due to H2 O2 treatment in egg white were also monitored. The influences from H2 O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n = 6). RESULTS: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T1 relaxation time in the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that produce no ROS, there was a small change in T1 due to H2 O2 itself (±1%), although a significant T2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T1 (13 ± 1%) and T2 (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 × 107 vs. 0.9 s-1 ·mM-1 ). Finally, significantly reduced T1 was observed in rotenone-treated mouse brain (5.1 ± 2.5%, P < 0.05). CONCLUSION: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.

Mapping brown adipose tissue based on fat water fraction provided by Z-spectral imaging.

BACKGROUND: Brown adipose tissue (BAT) has a great relevance in metabolic diseases and has been shown to be reduced in obesity and insulin resistance patients. Currently, Dixon MRI is used to calculate fat-water fraction (FWF) and differentiate BAT from white adipose tissue (WAT). However, it may fail in areas of phase wrapping and introduce fat-water swapping artifacts. PURPOSE: To investigate the capacity of the Z-spectrum imaging (ZSI) for the identification of BAT in vivo. STUDY TYPE: Retrospective study. SPECIMENS: WAT, BAT, and lean tissue from healthy mice. ANIMALS: Four C57BL/6 healthy mice. POPULATION: Five healthy volunteers. FIELD STRENGTH: 9.4T, 3T for volunteers. SEQUENCE: Z-Spectra data were fitted to a model with three Lorentzian peaks reflecting the direct saturation of tissue water (W) and methylene fat (F), and the magnetization transfer from the semi-solid tissues. The peak amplitudes of water and fat were used to map the FWF. The novel FWF metric was calibrated with an oil and water mixture phantom and validated in specimens, mice and human subjects. ASSESSMEMT: FWF distribution was compared with published works and values compared with Dixon's MRI results. STATISTICAL TESTS: Comparisons were performed by t-tests. RESULTS: ZSI clearly differentiated WAT, BAT, and lean tissues by having FWF = 1, 0.5, and 0, respectively. Calibration with oil mixture phantoms revealed a linear relationship between FWF and the actual fat fraction (R2 = 0.98). In vivo experiments in mice confirmed in vitro results by showing FWF = 0.6 in BAT. FWF maps of human subjects showed the same FWF distribution as Dixon's MRI (P > 0.05). ZSI is independent from B0 field inhomogeneity and fat-water swapping because both lipid and water frequency offsets are determined simultaneously during Z-spectral fitting. DATA CONCLUSION: ZSI can derive artifact-free FWF maps, which can be used to identify BAT distribution in vivo noninvasively. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1527-1533.

Influence of Free Radicals on the Intrinsic MRI Relaxation Properties.

Free radicals are critical contributors in various conditions including normal aging, Alzheimer's disease, cancer, and diabetes. Currently there is no non-invasive approach to image tissue free radicals based on endogenous contrast due to their extremely short lifetimes and low in vivo concentrations. In this study we aim at characterizing the influence of free radicals on the MRI relaxation properties. Phantoms containing free radicals were created by treating egg white with various H 2 O 2 concentrations and scanned on a 9.4 T MRI scanner at room temperature. T1 and T2 relaxation maps were generated from data acquired with an inversion recovery sequence with varied inversion times and a multi-echo spin echo sequence with varied echo times (TEs), respectively. Results demonstrated that free radicals express a strong shortening effect on T1, which was proportional to the H 2 O 2 concentration, and a relatively small reduction in T2 (<10%). Furthermore, the sensitivity of this approach in the detection of free radicals was estimated to be in the pM range that is within the physiological range of in vivo free radical expression. In conclusion, the free radicals show a strong paramagnetic effect that may be utilized as an endogenous MRI contrast for its non-invasive in vivo imaging.