Tissue T1 Relaxation Research Articles

DCE-Qnet: deep network quantification of dynamic contrast enhanced (DCE) MRI.

Quantification of dynamic contrast-enhanced (DCE)-MRI has the potential to provide valuable clinical information, but robust pharmacokinetic modeling remains a challenge for clinical adoption. A 7-layer neural network called DCE-Qnet was trained on simulated DCE-MRI signals derived from the Extended Tofts model with the Parker arterial input function. Network training incorporated B1 inhomogeneities to estimate perfusion (Ktrans, vp, ve), tissue T1 relaxation, proton density and bolus arrival time (BAT). The accuracy was tested in a digital phantom in comparison to a conventional nonlinear least-squares fitting (NLSQ). In vivo testing was conducted in ten healthy subjects. Regions of interest in the cervix and uterine myometrium were used to calculate the inter-subject variability. The clinical utility was demonstrated on a cervical cancer patient. Test-retest experiments were used to assess reproducibility of the parameter maps in the tumor. The DCE-Qnet reconstruction outperformed NLSQ in the phantom. The coefficient of variation (CV) in the healthy cervix varied between 5 and 51% depending on the parameter. Parameter values in the tumor agreed with previous studies despite differences in methodology. The CV in the tumor varied between 1 and 47%. The proposed approach provides comprehensive DCE-MRI quantification from a single acquisition. DCE-Qnet eliminates the need for separate T1 scan or BAT processing, leading to a reduction of 10 min per scan and more accurate quantification.

Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study.

Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8-week-old male offspring with PME (n = 7) and prenatal saline exposure (PSE) (n = 7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.

Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans. A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second. VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

P1585 Cardiac magnetic resonance estimated extracellular volume fraction, but not native T1 mapping, detects scar in patients referred for cardiac resynchronization therapy

Abstract Funding Acknowledgements The study was supported by Center for Cardiological Innovation Background Myocardial scar burden (focal fibrosis) is associated with poor response to cardiac resynchronization therapy (CRT), and should preferably be detected prior to device implantation. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is considered reference standard for scar detection, but is not available in renal failure. Diffuse fibrosis is assessed by T1 mapping CMR with or without calculation of extracellular volume fraction (ECV). The method is vulnerable to partial volume effects, thus subendocardial tissue is most often not included in mapping analyses. Whether the contrast-free native T1mapping could replace LGE in the preoperative evaluation of patients referred for CRT is unknown. Purpose To investigate if native T1 mapping and calculation of ECV can adequately detect scar in patients referred for CRT. Methods Scar was quantified as percentage segmental LGE in 45 patients (age 65 ± 10 years, 71% male, QRS-width 165 ± 17ms) referred for CRT. In total 720 segments were analyzed, and LGE≥50% was considered transmural scar. T1-mapping before and after contrast agent injection was performed in all patients. ECV was calculated based on the ratio between tissue T1 relaxation change and blood T1 relaxation change after contrast agent injection, corrected for the haematocrit level. The agreement between native T1/ECV and scar was evaluated with receiver operating characteristic (ROC) curves with calculation of area under the curve (AUC) and 95% confidence interval (CI). Results LGE was present in 255 segments, 465 segments were without LGE. Average native T1 in segments with LGE was 1028 ± 88 ms, and 1040 ± 60 ms in segments without LGE (p = 0.16). The corresponding numbers for ECV were 38.7 ± 10.9% and 30.0 ± 4.7%, p &amp;lt; 0.001. Native T1 showed poor agreement to scar independent of scar size (AUC = 0.532, 95% CI 0.485-0.578 for scars of all sizes, and AUC = 0.572, 95% CI 0.495-0.650 for transmural scars). ECV, on the other hand, showed reasonable agreement with scar of all sizes (AUC = 0.777, 95% CI 0.739-0.815), and good agreement with transmural scars (AUC = 0.856, 95% CI 0.811-0.902). (Figure) Conclusion The contrast-free CMR technique T1 mapping does not adequately detect scars in patients referred for CRT. Adding post contrast T1 measurements and calculating ECV improves accuracy, especially for transmural scars. Future studies should investigate if diffuse fibrosis could be predictive of CRT response. Abstract P1585 Figure. Detection of transmural scars

Slower Walking Speed Is Related to Early Femoral Trochlear Cartilage Degradation After ACL Reconstruction.

Post-traumatic patellofemoral osteoarthritis (OA) is prevalent after anterior cruciate ligament reconstruction (ACLR) and early cartilage degradation may be especially common in the femoral trochlear cartilage. Determining the presence of and factors associated with early femoral trochlear cartilage degradation, a precursor to OA, is a critical preliminary step in identifying those at risk for patellofemoral OA development and designing interventions to combat the disease. Early cartilage degradation can be detected using quantitative magnetic resonance imaging measures, such as tissue T2 relaxation time. The purposes of this study were to (i) compare involved (ACLR) versus uninvolved (contralateral) femoral trochlear cartilage T2 relaxation times 6 months after ACLR, and (ii) determine the relationship between walking speed and walking mechanics 3 months after ACLR and femoral trochlear cartilage T2 relaxation times 6 months after ACLR. Twenty-six individuals (age 23 ± 7 years) after primary, unilateral ACLR participated in detailed motion analyses 3.3 ± 0.6 months after ACLR and quantitative magnetic resonance imaging 6.3 ± 0.5 months after ACLR. There were no limb differences in femoral trochlear cartilage T2 relaxation times. Slower walking speed was related to higher (worse) femoral trochlear cartilage T2 relaxation times in the involved limb (Pearson's r: -0.583, p = 0.002) and greater interlimb differences in trochlear T2 relaxation times (Pearson's r: -0.349, p = 0.080). Walking mechanics were weakly related to trochlear T2 relaxation times. Statement of clinical significance: Slower walking speed was by far the strongest predictor of worse femoral trochlear cartilage health, suggesting slow walking speed may be an early clinical indicator of future patellofemoral OA after ACLR. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:645-652, 2020.

T2 relaxation times of the retrodiscal tissue in patients with temporomandibular joint disorders and in healthy volunteers: a comparative study

The aims of this study were to compare the temporomandibular joint (TMJ) retrodiscal tissue T2 relaxation times between patients with temporomandibular disorders (TMDs) and asymptomatic volunteers and to assess the diagnostic potential of this approach. Patients with TMD (n = 173) and asymptomatic volunteers (n = 17) were examined by using a 1.5-T magnetic resonance scanner. The imaging protocol consisted of oblique sagittal, T2-weighted, 8-echo fast spin echo sequences in the closed mouth position. Retrodiscal tissue T2 relaxation times were obtained. Additionally, disc location and reduction, disc configuration, joint effusion, osteoarthritis, and bone edema or osteonecrosis were classified using MRI scans. The T2 relaxation times of each group were statistically compared. Retrodiscal tissue T2 relaxation times were significantly longer in patient groups than in asymptomatic volunteers (P < .01). T2 relaxation times were significantly longer in all of the morphologic categories. The most important variables affecting retrodiscal tissue T2 relaxation times were disc configuration, joint effusion, and osteoarthritis. Retrodiscal tissue T2 relaxation times of patients with TMD were significantly longer than those of healthy volunteers. This finding may lead to the development of a diagnostic marker to aid in the early detection of TMDs.

Quantitative T2-mapping using MRI for detection of prostate malignancy: a systematic review of the literature.

Quantitative T2-mapping using magnetic resonance imaging (MRI) allows measurement of tissue T2-relaxation times to complement anatomical and spatial information derived from T2-weighted imaging. Studies have shown varying T2-relaxation times between prostate malignancy and non-malignant prostatic tissue. This paper aims to critically review the literature in a systematic review, to determine the usefulness of T2-mapping in the evaluation of prostate malignancy. A literature search of PubMed and Embase databases was performed. There were 17 studies, up to 31 June 2018, that measured T2-relaxation times of prostate cancer and non-malignant prostatic tissue. Data reviewed from each study included: number of patients and regions of interest evaluated; patient age; study design; T2-mapping technique utilized; reported T2-relaxation values; method of data analysis; method of “ground-truth” assessment; and reported limitations. The T2-relaxation times of prostate cancer and non-malignant prostatic tissue were compared. The T2-relaxation times in the transition zone (TZ) are generally lower than the peripheral zone (PZ). The T2-relaxation times in prostate malignancy are significantly lower than normal PZ in all the studies that performed a statistical comparison. In three out of four studies that performed a statistical comparison, there was no significant difference in the T2-relaxation times between prostate malignancy and non-malignant TZ. T2-mapping appears useful in identifying prostate malignancy in the peripheral zone but is unable to reliably distinguish prostate malignancy and non-malignant transition zone. Further studies are recommended to determine if T2-mapping can improve diagnostic accuracy when used in conjunction with multiparametric MRI for detection of prostate malignancy.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint

Background: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). Purpose: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients’ level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. Results: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. Conclusion: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial

ObjectiveThe efficacy and safety of BST-CarGel®, a chitosan scaffold for cartilage repair was compared with microfracture alone at 1 year during a multicenter randomized controlled trial in the knee. This report was undertaken to investigate 5-year structural and clinical outcomes.DesignThe international randomized controlled trial enrolled 80 patients, aged 18 to 55 years, with grade III or IV focal lesions on the femoral condyles. Patients were randomized to receive BST-CarGel® treatment or microfracture alone, and followed standardized 12-week rehabilitation. Co-primary endpoints of repair tissue quantity and quality were evaluated by 3-dimensional MRI quantification of the degree of lesion filling (%) and T2 relaxation times. Secondary endpoints were clinical benefit measured with WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaires and safety. General estimating equations were used for longitudinal statistical analysis of repeated measures.ResultsBlinded MRI analysis demonstrated that BST-CarGel®-treated patients showed a significantly greater treatment effect for lesion filling (P = 0.017) over 5 years compared with microfracture alone. A significantly greater treatment effect for BST-CarGel® was also found for repair tissue T2 relaxation times (P = 0.026), which were closer to native cartilage compared to the microfracture group. BST-CarGel® and microfracture groups showed highly significant improvement at 5 years from pretreatment baseline for each WOMAC subscale (P < 0.0001), and there were no differences between the treatment groups. Safety was comparable for both groups.ConclusionsBST-CarGel® was shown to be an effective mid-term cartilage repair treatment. At 5 years, BST-CarGel® treatment resulted in sustained and significantly superior repair tissue quantity and quality over microfracture alone. Clinical benefit following BST-CarGel® and microfracture treatment were highly significant over baseline levels.

Rapid Parametric Mapping of the Longitudinal Relaxation Time T1 Using Two-Dimensional Variable Flip Angle Magnetic Resonance Imaging at 1.5 Tesla, 3 Tesla, and 7 Tesla

IntroductionVisual but subjective reading of longitudinal relaxation time (T1) weighted magnetic resonance images is commonly used for the detection of brain pathologies. For this non-quantitative measure, diagnostic quality depends on hardware configuration, imaging parameters, radio frequency transmission field (B1+) uniformity, as well as observer experience. Parametric quantification of the tissue T1 relaxation parameter offsets the propensity for these effects, but is typically time consuming. For this reason, this study examines the feasibility of rapid 2D T1 quantification using a variable flip angles (VFA) approach at magnetic field strengths of 1.5 Tesla, 3 Tesla, and 7 Tesla. These efforts include validation in phantom experiments and application for brain T1 mapping.MethodsT1 quantification included simulations of the Bloch equations to correct for slice profile imperfections, and a correction for B1+. Fast gradient echo acquisitions were conducted using three adjusted flip angles for the proposed T1 quantification approach that was benchmarked against slice profile uncorrected 2D VFA and an inversion-recovery spin-echo based reference method. Brain T1 mapping was performed in six healthy subjects, one multiple sclerosis patient, and one stroke patient.ResultsPhantom experiments showed a mean T1 estimation error of (-63±1.5)% for slice profile uncorrected 2D VFA and (0.2±1.4)% for the proposed approach compared to the reference method. Scan time for single slice T1 mapping including B1+ mapping could be reduced to 5 seconds using an in-plane resolution of (2×2) mm2, which equals a scan time reduction of more than 99% compared to the reference method.ConclusionOur results demonstrate that rapid 2D T1 quantification using a variable flip angle approach is feasible at 1.5T/3T/7T. It represents a valuable alternative for rapid T1 mapping due to the gain in speed versus conventional approaches. This progress may serve to enhance the capabilities of parametric MR based lesion detection and brain tissue characterization.

Time course of the effect of ferumoxytol on T1-relaxation times of blood, liver, myocardium, and acute infarction

Background Intravenous iron-supplementation drugs are frequently used for treatment of iron-deficiency anemia in chronic kidney disease. Some iron-agents alter tissue T1-relaxation times (T1) for days after administration, and could obscure MRI diagnosis. Conversely, these agents may have the potential to delineate pathology. We sought to investigate the T1-shortening effect of ferumoxytol and iron-dextran, determine how T1 of blood, liver, and myocardium change over time in-vivo after iron administration, and explore the utility of these agents for imaging acute myocardial infarction (MI). Methods We determined in-vitro T1 of ferumoxytol and irondextran (20mg Fe ad 500ml 0.9%NaCl). Seven dogs with acute, reperfused MI were scanned five days later on a 3.0T MRI-scanner, at which time ferumoxytol (n=5) or iron-dextran (n=2) was administered in clinically used doses (approx. 130mg iron). Inversion-recovery, gradient-echo images with various inversion-times (1151600ms) were acquired prior to and serially after ironinjection at multiple time-points on day 1 (n=7), 2 (n=5), 3 (n=2), and 7 (n=7). T1 was determined by standard curve-fitting. Results In-vitro T1 of ferumoxytol and iron-dextran were 13% and 89% of 0.9%NaCl, respectively. T1 of blood, myocardium, and liver were 2027±421ms, 1384±143ms, and 806±74ms, respectively. Results for ferumoxytol were: T1 of blood dropped to 7% (p 0.05). Conclusions Ferumoxytol may affect cardiovascular MR beyond 2 days and liver MR beyond 1 week after administration of doses used clinically for iron-deficiency anemia. Unless recognized, this could affect MRI diagnosis. The differential kinetics suggest a potential use of ferumoxytol for delineation of acute MI.

Kinetic assessment of breast tumors using high spatial resolution signal enhancement ratio (SER) imaging

The goal of this study was to investigate the relationship between an empirical contrast kinetic parameter, the signal enhancement ratio (SER), for three-timepoint, high spatial resolution contrast-enhanced (CE) MRI, and a commonly analyzed pharmacokinetic parameter, kep, using dynamic high temporal resolution CE-MRI. Computer simulation was performed to investigate: 1) the relationship between the SER and the contrast agent concentration ratio (CACR) of two postcontrast timepoints (tp1 and tp2); 2) the relationship between the CACR and the redistribution rate constant (kep) based on a two-compartment pharmacokinetic model; and 3) the sensitivity of the relationship between the SER and kep to native tissue T1 relaxation time, T10, and to errors in an assumed vascular input function. The relationship between SER and kep was verified experimentally using a mouse model of breast cancer. The results showed that a monotonic mathematical relationship between SER and kep could be established if the acquisition parameters and the two postinjection timepoints of SER, tp1, tp2, were appropriately chosen. The in vivo study demonstrated a close correlation between SER and kep on a pixel-by-pixel basis (Spearman rank correlation coefficient=0.87+/-0.03). The SER is easy to calculate and may have a unique role in breast tissue characterization.

Erythropoietin Protects from Post-Traumatic Edema in the Rat Brain

Erythropoietin (Epo) is gaining interest in various neurological insults as a possible neuroprotective agent. We determined the effects of recombinant human Epo (rhEpo, 5000 IU per kg bw) on brain edema induced in rats by traumatic brain injury (TBI; impact-acceleration model; rhEpo administration 30 mins after injury). Magnetic resonance imaging (MRI) and a gravimetric technique were applied. In the MRI experiments, the apparent diffusion coefficient (ADC) and the tissue T(1) relaxation time were measured hourly in the neocortex and caudoputamen, during a 6 h time span after TBI. In the gravimetric experiments, brain water content (BWC) was determined in these two regions, 6 h after TBI. Apparent diffusion coefficient measurements showed that rhEpo decreased brain edema early and durably. Gravimetric measurements showed that rhEpo decreased BWC at H(6) in the neocortex as well as in the caudoputamen. No significant differences in ADC, in T(1), or in BWC were found between rhEpo treated-TBI rats and sham-operated rats. Our findings show that post-traumatic administration of rhEpo can significantly reduce the development of brain edema in a model of diffuse TBI. Further studies should be conducted to identify the biochemical mechanisms involved in these immediate effects and to assess the use of rhEpo as a possible therapy for post-traumatic brain edema.

Quantification of fluid changes in rat leg joints with adjuvant arthritis by a one‐dimensional magnetic resonance imaging experiment

A simple and reliable method for quantifying the fluid content and characterizing the tissue T2 relaxation properties of animal extremities has been devised. This one-dimensional magnetic resonance imaging experiment, applied to the adjuvant arthritis model in rats, provides a useful, noninvasive monitor of the course of the disease in vivo. Tissue is characterized through the analysis of the biexponential T2 decay of the NMR-active hydrogen in the rat leg joint tissue. Long and short T2 components are identified, both of which are sensitive to the arthritic process. The long component is suggested to come from edema and increases by a factor of ca. 9 during the course of the disease, whereas the short T2 component may represent cellular influx into the joint and increases by a factor of ca. 3. These changes correlate with the severity of the disease and can be used to monitor therapeutic response. The main advantage of the technique over the more traditional two-dimensional imaging approach is that only one spatial variable has to be resolved, resulting in shorter imaging time.

Frequency dependence of magnetic resonance spin-lattice relaxation of protons in biological materials.

The frequency dependence of spin-lattice (T1) relaxation times of protons in tissues and other macromolecular solutions was investigated. This dependence can be principally assigned to reduced mobility of water molecules "hydrated" on the surface of macromolecular structures. The T1 relaxation time of "hydration water" was found to increase linearly with frequency in the range from 5 to 100 MHz (T1 = 1.83 f + 25.0). It is assumed that the remainder of water in the tissue has a relaxation rate that is independent of frequency, as is characteristic of bulk tap water. Variations occur in the fraction of water hydrated or bound from one organ to the next. As the observed relaxation rate is a weighted average of the two rates as described by the fast exchange model, the above empirical relationship can be used to take a tissue T1 relaxation time measured at one frequency and then calculate the tissue T1 relaxation time that would be expected at another frequency. Good agreements were obtained between such calculated tissue T1 values and the T1 values actually measured at the second frequency. Variations between the calculated and measured T1 values in some classes of tissues indicate that there are also less important secondary factors such as lipid content.