Imaging-based assessment of fatty acid composition in human bone marrow adipose tissue at 7 T: Method comparison and in vivo feasibility.

PURPOSE: To demonstrate the feasibility and accuracy of chemical shift-encoded imaging of the fatty acid composition (FAC) of human bone marrow adipose tissue at 7 T, and to determine suitable image-acquisition parameters using simulations. METHODS: The noise performance of FAC estimation was investigated using simulations with a range of inter-echo time, and accuracy was assessed using a phantom experiment. Furthermore, one knee of 8 knee-healthy subjects (ages 35-54 years) was imaged, and the fractions of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) were mapped. Values were compared between reconstruction methods, and between anatomical regions. RESULTS: Based on simulations, ΔTE = 0.6 ms was chosen. The phantom experiment demonstrated high accuracy of especially SFA using a constrained reconstruction model (slope = 1.1, average bias = -0.2%). The lowest accuracy was seen for PUFA using a free model (slope = 2.0, average bias = 9.0%). For in vivo images, the constrained model resulted in lower intersubject variation compared with the free model (e.g., in the femoral shaft, the SFA percent-point range was within 1.0% [vs. 3.0%]). Furthermore, significant regional FAC differences were detected. For example, using the constrained approach, the femoral SFA in the medial condyle was lower compared with the shaft (median [range]: 27.9% [27.1%, 28.4%] vs. 32.5% [31.8%, 32.8%]). CONCLUSION: Bone marrow adipose tissue FAC quantification using chemical-shift encoding is feasible at 7 T. Both the noise performance and accuracy of the technique are superior using a constrained signal model.

Favorable fatty acid composition in adipose tissue in healthy Iraqi- compared to Swedish-born men - a pilot study using MRI assessment.

Middle Eastern immigrants are at high-risk for insulin resistance. Fatty acid composition (FAC) plays an important role in the development of insulin resistance but has not been investigated in people of Middle Eastern ancestry. Here, the aim was to assess the FAC in visceral and subcutaneous adipose tissue (VAT and SAT) in healthy Iraqi- and Swedish-born men using a magnetic resonance imaging (MRI) method.This case-control study included 23 Iraqi- and 15 Swedish-born middle-aged men, without cardiometabolic disease. Using multi-echo MRI of the abdomen, the fractions of saturated, monounsaturated, and polyunsaturated fatty acids (fSFA, fMUFA, and fPUFA) were estimated in VAT and SAT. SAT was further analyzed in deep and superficial compartments (dSAT and sSAT).In all depots, fPUFA was significantly higher and fSFA significantly lower in Iraqi men, independently of age and BMI. In both Iraqi- and Swedish-born men, higher fPUFA and lower fMUFA were found in sSAT vs. dSAT. Among Iraqi men only, higher fPUFA and lower fMUFA were found in SAT vs. VAT.Iraqi-born men presented a more favorable abdominal FAC compared to Swedish-born men. This MRI method also revealed different FACs in different abdominal depots. Our results may reflect a beneficial FAC in Middle Eastern immigrants.

Quantitative 1 H MRI and MRS of fatty acid composition.

Adipose tissue as well as other depots of fat (triglycerides) are increasingly being recognized as active contributors to the human function and metabolism. In addition to the fat concentration, also the fatty acid chemical composition (FAC) of the triglyceride molecules may play an important part in diseases such as obesity, insulin resistance, hepatic steatosis, osteoporosis, and cancer. MR spectroscopy and chemical-shift-encoded imaging (CSE-MRI) are established methods for non-invasive quantification of fat concentration in tissue. More recently, similar techniques have been developed for assessment also of the FAC in terms of the number of double bonds, the fraction of saturated, monounsaturated, and polyunsaturated fatty acids, or semi-quantitative unsaturation indices. The number of papers focusing on especially CSE-MRI-based techniques has steadily increased during the past few years, introducing a range of acquisition protocols and reconstruction algorithms. However, a number of potential sources of bias have also been identified. Furthermore, the measures used to characterize the FAC using both MRI and MRS differ, making comparisons between different techniques difficult. The aim of this paper is to review MRS- and MRI-based methods for in vivo quantification of the FAC. We describe the chemical composition of triglycerides and discuss various potential FAC measures. Furthermore, we review acquisition and reconstruction methodology and finally, some existing and potential applications are summarized. We conclude that both MRI and MRS provide feasible non-invasive alternatives to the gold standard gas chromatography for in vivo measurements of the FAC. Although both are associated with gas chromatography, future studies are warranted.

In vivo comparison of MRI-based and MRS-based quantification of adipose tissue fatty acid composition against gas chromatography.

PURPOSE: To compare MR-based fatty acid composition (FAC) quantification methods against the gold standard technique, gas chromatography (GC), with comparison of a free and a constrained signal model. The FAC was measured in the healthy and edematous legs of lymphedema patients. METHODS: In vivo MRS and MRI data were acquired from 19 patients at 3 T. Biopsies were collected from subcutaneous adipose tissue of both thighs during liposuction. The saturated, monounsaturated, and polyunsaturated fatty acid fractions (fSFA , fMUFA and fPUFA , respectively) were estimated with the MR-based methods using two signal models: free and constrained (number of methylene-interrupted double bonds expressed in number of double bonds, based on GC data). Linear regression, Bland-Altman plots, and correlation coefficients were used to evaluate the MR methods against the GC of the biopsies. Paired t-test was used to compare the FAC difference between edematous and healthy legs. RESULTS: The estimated parameters correlated well with the GC data (rSFA , rMUFA , and rPUFA = 0.82, 0.81 and 0.89, respectively) using the free model MRI-based approach. In comparison, the MRS-based method resulted in weaker correlations and larger biases compared with MRI. In both cases, correct estimation of fMUFA and fPUFA fractions were not possible using the constrained model. The difference in FAC of healthy and edematous legs were estimated to 0.008 (P = .01), -0.009 (P = .005), and 0.002 (P = .03) for fSFA , fMUFA , and fPUFA . CONCLUSION: In this study, MRI-based FAC quantification was highly correlated, although slightly biased, compared with GC, whereas the MRS-based approach resulted in weaker correlations. Small but significant differences could be found between the healthy and edematous legs of lymphedema patients using GC analysis.

The role of cartilage glycosaminoglycan structure in gagCEST.

Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.

Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology.

BACKGROUND: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis. OBJECTIVE: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology. METHODS: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2* were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining. RESULTS: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2*: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2*: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2*: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures. CONCLUSIONS: MR relaxation times T1, T2 and T2* of ex vivo human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed in vivo, MR relaxation times may thus be potential biomarkers for meniscus degeneration.

Is good muscle function a protective factor for early signs of knee osteoarthritis after anterior cruciate ligament reconstruction? The SHIELD cohort study protocol.

Introduction: Knee injury history and increased joint load, respectively, are major risk factors for the development of knee osteoarthritis (OA). Lower extremity muscle function, such as knee muscle strength, influence joint load and may be important for the onset of knee OA. However, the role of muscle function as a possible modifiable protective mechanism for the development of OA after anterior cruciate ligament reconstruction (ACLR) is not clear. Methods and analysis: In this prospective cohort study, 100 patients (50% women, 18-35 years) with ACLR will be recruited from Skåne University Hospital, Sweden and Oslo University Hospital, Norway. They will be assessed with a comprehensive test battery of muscle function including muscle strength, muscle activation, hop performance, and postural orientation as well as patient-reported outcomes, one year (baseline) and three years (follow-up) after ACLR. Primary predictor will be knee extension strength, primary outcome will be patient-reported knee pain (Knee injury and Osteoarthritis Outcome Score, subscale pain) and secondary outcomes include compositional MRI (T2 mapping) and turnover of cartilage and bone biomarkers. Separate linear regression model will be used to elucidate the influence of each baseline muscle function variable on the outcomes at follow-up, adjusted for baseline values. Twenty non-injured individuals will also be assessed with MRI. This study is approved by The Regional Ethical Review Board in Lund (Sweden) and Oslo (Norway). Discussion: This study may have important clinical implications for using muscle function to screen for risk of early-onset knee OA and for optimizing exercise therapy after knee injury.

T2 relaxation time bias in gagCEST at 3T and 7T: comparison of saturation schemes.

PURPOSE: To characterize the effects of water T2 relaxation time in the glycosaminoglycan chemical exchange saturation transfer method (gagCEST) and compare them between 3T and 7T as well as between various saturation schemes. METHODS: Simulations and a phantom experiment were conducted at 3T and 7T in a range of water T2 values and GAG concentrations using various saturation schemes. For both simulations and MRI measurements, unsaturated signal as well as the saturated Z-spectrum were generated, and the magnetization transfer ratio asymmetry at 1 parts per million was used as a measure of the gagCEST effect size. RESULTS: The simulations and phantom experiment results showed a clear GAG concentration and T2 dependence of the gagCEST effect size. Whereas the gagCEST effect size was much larger at 7T, the impact of the T2 bias was more pronounced at 3T. The saturation train length, duty cycle, and average B1 all had clear impact on both the gagCEST effect size and T2 bias. CONCLUSION: The water T2 relaxation is important to consider in gagCEST, especially at 3T. The T2 differences can introduce a pronounced bias, which may obscure the gagCEST effect when using low duty cycles and long saturation trains.

Assessment of Subfascial Muscle/Water and Fat Accumulation in Lymphedema Patients Using Magnetic Resonance Imaging.

Background: In patients with arm or leg lymphedema, more fat has been found in the epifascial compartment of the edematous limb compared to the healthy limb. However, not much is known about subfascial fat accumulation in these patients. This study aims to investigate the intramuscular and intermuscular fat and muscle/water volume in lymphedema patients. The excess of intramuscular and intermuscular fat volume was also compared to the excess epifascial fat volume, the excess limb volume, and the duration of lymphedema. Methods and Results: Data from 13 patients (seven arm and six leg lymphedemas) were acquired using a 1.5 T magnetic resonance imaging (MRI) scanner before liposuction and at five time points (4 days, 4 weeks, 3 months, 6 months, and 1 year) after liposuction. From water-fat imaging, fat and muscle/water volumes within the intramuscular and intermuscular compartments were calculated. The relative excess volume was defined as (volume of edematous limb-volume of healthy limb)/volume of healthy limb. Elevated relative excess volumes of intramuscular and intermuscular fat were found at all time points. A decrease in the relative excess volume of muscle/water over time was found. This decrease was not correlated to the relative excess of epifascial fat volume, the relative excess of limb volume, or the duration of lymphedema. Conclusions: An excess fat volume was found in the intramuscular and intermuscular compartments in lymphedema patients. The results suggest that the subfascial compartment needs to be studied separately as no correlation between intramuscular/intermuscular fat accumulation and other measured parameters was found.

Knee dGEMRIC at 7 T: comparison against 1.5 T and evaluation of T1-mapping methods.

BACKGROUND: dGEMRIC (delayed Gadolinium Enhanced Magnetic Resonance Image of Cartilage) is a well-established technique for cartilage quality assessment in osteoarthritis at clinical field strengths. The method is robust, but requires injection of contrast agent and a cumbersome examination procedure. New non-contrast-agent-based techniques for cartilage quality assessment are currently being developed at 7 T. However, dGEMRIC remains an important reference technique during this development. The aim of this work was to compare T1 mapping for dGEMRIC at 7 T and 1.5 T, and to evaluate three T1-mapping methods at 7 T. METHODS: The knee of 10 healthy volunteers and 9 patients with early signs of cartilage degradation were examined at 1.5 T and 7 T after a single (one) contrast agent injection (Gd-(DTPA)2-). Inversion recovery (IR) sequences were acquired at both field strengths, and at 7 T variable flip angle (VFA) and Look-Locker (LL) sequences were additionally acquired. T1 maps were calculated and average T1 values were estimated within superficial and deep regions-of-interest (ROIs) in the lateral and medial condyles, respectively. RESULTS: T1 values were 1.8 (1.4-2.3) times longer at 7 T. A strong correlation was detected between 1.5 T and 7 T T1 values (r = 0.80). For IR, an additional inversion time was required to avoid underestimation (bias±limits of agreement - 127 ± 234 ms) due to the longer T1 values at 7 T. Out of the two 3D sequences tested, LL resulted in more accurate and precise T1 estimation compared to VFA (average bias±limits of agreement LL: 12 ± 202 ms compared to VFA: 25 ± 622 ms). For both, B1 correction improved agreement to IR. CONCLUSION: With an adapted sampling scheme, dGEMRIC T1 mapping is feasible at 7 T and correlates well to 1.5 T. If 3D is to be used for T1 mapping of the knee at 7 T, LL is preferred and VFA is not recommended. For VFA and LL, B1 correction is necessary for accurate T1 estimation.

Lymphedema Leads to Fat Deposition in Muscle and Decreased Muscle/Water Volume After Liposuction: A Magnetic Resonance Imaging Study.

BACKGROUND: Lymphedema leads to adipose tissue deposition. Water-fat magnetic resonance imaging (MRI) can quantify and localize fat and water. The presence of excess fat and excess water/muscle in the subfascial compartment of the lymphedematous limb has not been investigated before. The aim of this study was to investigate epifascial and subfascial fat and water contents in patients with chronic lymphedema before and after liposuction. METHODS AND RESULTS: Seven patients with arm lymphedema and six with leg lymphedema were operated on. The limbs were examined with water-fat MRI before liposuction (baseline) and at five time points. Complete reduction of the excess limb volumes was achieved. The excess epifascial fat was evident in the edematous limbs and a drop was seen following surgery. There were differences in excess water at all time points. At 1 year there was a decrease in excess water. Excess subfascial fat was seen in the edematous limbs at all time points. Subfascial excess water/muscle did not show any differences after surgery. However, starting from 3 months there was less subfascial water/muscle compared with baseline. CONCLUSIONS: Subfascial fat in the lymphedematous limbs did not change. In contrast, the water in the subfascial compartment was reduced over time, which may represent a decrease of muscle volume after treatment due to less mechanical load after liposuction. Using water-fat MRI-based fat quantification, the fat and water contents may be quantified and localized in the various compartments in lymphedema.

High-Resolution MR Imaging of Muscular Fat Fraction-Comparison of Three T2-Based Methods and Chemical Shift-Encoded Imaging.

Chemical shift-encoded imaging (CSEI) is the most common magnetic resonance imaging fat-water separation method. However, when high spatial resolution fat fraction (FF) images are desired, CSEI might be challenging owing to the increased interecho spacing. Here, 3 T2-based methods have been assessed as alternative methods for obtaining high-resolution FF images. Images from the calf of 10 healthy volunteers were acquired; FF maps were then estimated using 3 T2-based methods (2- and 3-parameter nonlinear least squares fit and a Bayesian probability method) and CSEI for reference. In addition, simulations were conducted to characterize the performance of various methods. Here, all T2-based methods resulted in qualitatively improved high-resolution FF images compared with high-resolution CSEI. The 2-parameter fit showed best quantitative agreement to low-resolution CSEI, even at low FF. The estimated T2-values of fat and water, and the estimated muscle FF of the calf, agreed well with previously published data. In conclusion, T2-based methods can provide improved high-resolution FF images of the calf compared with the CSEI method.

Fat quantification in skeletal muscle using multigradient-echo imaging: Comparison of fat and water references.

PURPOSE: To investigate the precision, accuracy, and repeatability of water/fat imaging-based fat quantification in muscle tissue using a large flip angle (FA) and a fat reference for the calculation of the proton density fat fraction (FF). Comparison is made to a small FA water reference approach. MATERIALS AND METHODS: An Intralipid phantom and both forearms of six patients suffering from lymphedema and 10 healthy volunteers were investigated at 1.5T. Two multigradient-echo sequences with eight echo times and FAs of 10° and 85° were acquired. For healthy volunteers, the acquisition of the right arm was performed twice with repositioning. From each set, water reference FF and fat reference FF images were reconstructed and the average FF and the standard deviation were calculated within the subfascial compartment. The small FA water reference was considered the reference standard. RESULTS: A high agreement was found between the small FA water reference and large FA fat reference methods (FF bias = 0.31%). In this study, the large FA fat reference approach also resulted in higher precision (38% smaller FF standard deviation in homogenous muscle tissue), but no significant difference in repeatability between the various methods was detected (coefficient of repeatability of small FA water reference approach 0.41%). CONCLUSION: The precision of fat quantification in muscle tissue can be increased with maintained accuracy using a larger flip angle, if a fat reference instead of a water reference is used.

Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls.

INTRODUCTION: Children with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. METHODS: Hepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. RESULTS: No children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). CONCLUSIONS: In children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver.

Relaxation effects in MRI-based quantification of fat content and fatty acid composition.

PURPOSE: To investigate various sources of bias in MRI-based quantification of fat fraction (FF) and fatty acid composition (FAC) using chemical shift-encoded techniques. METHODS: Signals from various FFs and FACs and individual relaxation rates of all signal components were simulated. From these signals, FF and FAC parameters were estimated with and without correction for differences in individual relaxation rates. In addition, phantom experiments were conducted with various flip angles and number of echoes to validate the simulations. RESULTS: As expected, T(1) weighting resulted in an overestimation of the FF, but had much smaller impact on the FAC parameters. Differences in T(2) values of the signal components resulted in overestimation of the FAC parameters in fat/water mixtures, whereas the estimation in pure oil was largely unaffected. This bias was corrected using a simplified signal model with different T(2) values of water and fat, where the accuracy of the modeled T(2) of water was critical. The results of the phantom experiment were in agreement with simulations. CONCLUSION: T(1) weighting has only a minor effect on FAC quantification in both fat/water mixtures and pure oils. T(2) weighting is mainly a concern in fat/water mixtures but may be corrected using a simplified model.

Fat quantification using multiecho sequences with bipolar gradients: investigation of accuracy and noise performance.

PURPOSE: To investigate the accuracy and noise performance of fat quantification with multiple gradient-echo images acquired using bipolar read-out gradients and compare them with those of the well-established unipolar technique. THEORY: The bipolar read-out technique induces phase and amplitude errors caused by gradient delays, eddy currents, and frequency-dependent coil sensitivity. In this study, these errors were corrected for jointly with the fat/water separation by modeling the impact of these effects on the signal. This approach did not require acquisition of reference data or modification of the pulse sequence. METHODS: Simulations and a phantom experiment were used to investigate the accuracy and noise performance of the technique and compare them with those of a well-established technique using unipolar read-out gradients. Also, the in vivo feasibility was demonstrated for abdominal applications. RESULTS: The phantom experiment demonstrated similar accuracy of the bipolar and unipolar fat quantification techniques. In addition, the noise performance was shown not to be affected by the added estimations of the phase and amplitude errors for most inter-echo times. CONCLUSION: The bipolar technique was found to provide accurate fat quantification with noise performance similar to the unipolar technique given an appropriate choice of inter-echo time.

Simultaneous quantification of fat content and fatty acid composition using MR imaging.

Not only the fat content but also the composition of fatty acids (FAs) in stored triglycerides might be of interest in the research on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. In this study, a novel reconstruction approach is proposed that uses theoretical knowledge of the chemical structure of FAs to simultaneously quantify the fat fraction (FF) and the FAs composition (chain length cl, number of double bonds ndb, and number of methylene-interrupted double bonds nmidb) from multiple gradient echo images. Twenty phantoms with various fat contents (FF = 9-100%) and FA compositions (cl = 12.1-17.9, ndb = 0.23-5.10, and nmidb = 0.04-2.39) were constructed and imaged in a 3-T Siemens scanner. In addition, spectra were acquired in each phantom. Slopes and "standard deviations from true values" were used to investigate the accuracy of the two methods. The imaging method holds well in a comparison to the previously suggested spectroscopy method and showed similar overall accuracy. The in vivo feasibility was demonstrated in the thigh adipose tissue of a healthy volunteer. In conclusion, our developed method is a promising tool for FF and FA composition quantification.

Quantification of low fat contents: a comparison of MR imaging and spectroscopy methods at 1.5 and 3 T.

Magnetic resonance spectroscopy (MRS) has long been considered the golden standard for non-invasive measurement of tissue fat content. With improved techniques for fat/water separation, imaging has become an alternative to MRS for fat quantification. Several imaging models have been proposed, but their performance relative to MRS at very low fat contents is yet not fully established. In this work, imaging and spectroscopy were compared at 1.5 T and 3 T in phantoms with 0-3% fat fraction (FF). We propose a multispectral model with individual a priori R(2) relaxation rates for water and fat, and a common unknown R(2)' relaxation. Magnitude and complex image reconstructions were also compared. Best accuracy was obtained with the imaging method at 1.5 T. At 3 T, the FFs were underestimated due to larger fat-water phase shifts. Agreement between measured and true FF was excellent for the imaging method at 1.5 T (imaging: FF(meas)=0.98 FF(true)-0.01%, spectroscopy: FF(meas)=0.77 FF(true)+0.08%), and fair at 3 T (imaging: FF(meas)=0.91 FF(true)-0.19%, spectroscopy: FF(meas)=0.79 FF(true)+0.02%). The imaging method was able to quantify FFs down to approx. 0.5%. We conclude that the suggested imaging model is capable of fat quantification with accuracy and precision similar to or better than spectroscopy and offers an improvement vs. a model with a common R(2)* relaxation only.

Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone.

This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected (125)I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting (125)I-labeled PSA30. Tissue uptake of (125)I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, (18)F-fluoro-deoxy-glucose ((18)F-FDG) or (18)F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high (125)I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either (18)F-FDG or (18)F-choline. Biodistribution of (125)I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24-48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women.

Persistent human papillomavirus (HPV) infection is a prerequisite for cervical cancer and results from bypassing the local immune response. Twenty-four volunteers underwent an ectocervical biopsy, Pap smear, tests for sexually transmitted infections including HIV and HPV genotyping. All answered a questionnaire regarding medical history. Repeat Pap smear and HPV genotyping was performed 9-26 months later. Quantitative reverse transcriptase (qRT-)PCR was used to assess expression of CD3, CD4, CD8, CD19, CD27, IL-2, IL-12, IL-4, IL-10, IL-17, HLA-DRα, TGFß, IFNγ, PD-1, PD-L1, CTLA-4, LAG3, IgA, IgG, CCR5, CCL5/RANTES and the IL-7 receptor in the biopsies. Eleven of 24 volunteers were HPV DNA-positive at baseline. Four of 10 were infected with a persistent HPV genotype at follow-up. All target molecules were successfully amplified and quantified except for IL-4. We found no difference in mRNA expression of these molecules when comparing HPV DNA-positive and -negative women, neither when comparing persistently infected individuals or those who cleared the infection. However, mRNA expression of the B cell phenotypic marker CD19 was higher in women using hormonal contraception than those not (p<0.05). HPV infection does not evoke a local inflammatory immune response in the ectocervix measurable with qRT-PCR. Hormonal contraception may influence B cell activity in the cervix.