"How to navigate this new area": Intensive care clinicians' perceptions of voluntary assisted dying in the intensive care unit: A multisite exploratory study.

BACKGROUND: There is growing momentum worldwide for assisted dying. In Australia, voluntary assisted dying may occur in any setting, including an intensive care unit (ICU). As the subject of much debate worldwide, exploring ICU clinicians' perceptions of assisted dying is essential. AIM: The aim of this study was to explore clinicians' perceptions of and preparedness for voluntary assisted dying in the ICU. METHOD: An exploratory qualitative descriptive design using individual interviews was used. Medical, nursing, and allied health clinicians from three ICUs were recruited. Interviews were conducted between Nov 2022 and Jan 2023, with a hypothetical scenario about voluntary assisted dying used to prompt discussion. Interviews were recorded, professionally transcribed, and analysed using inductive content analysis. FINDINGS: ICU registered nurses (n = 20), physicians (n = 2), and allied health clinicians (n = 4) participated with interviews lasting 18-45 min (mean: 28 min). Analysis revealed four themes: (i) purpose of ICU reflected that ICU care was not all about saving lives, yet recognising dying and changing priorities was challenging; (ii) dying in the ICU is complex due to difficulties in talking about dying, accepting death as the outcome and evaluating care efficacy; (iii) voluntary assisted dying is a lot of grey because of perceived clinical and ethicolegal challenges; and finally, (iv) respecting choice was about respecting patients' values, beliefs, and autonomy, as well as clinicians' beliefs and right to exercise autonomy through conscientious objection. CONCLUSION: Dying and death are inevitable, and views and perspectives about assisted dying will continue to evolve. Respecting patient choice is at the core of assisted dying, but respecting clinicians' perspectives and choice is equally important. With voluntary assisted dying now legal in all Australian states, ensuring ICU team and individual clinician preparedness through access to education, resources, and specialist support services is key to raising awareness and easing uncertainty about deaths through voluntary assisted dying.

Regulation of Escherichia coli fim gene transcription by GadE and other acid tolerance gene products.

Uropathogenic Escherichia coli (UPEC) cause millions of urinary tract infections each year in the United States. Type 1 pili are important for adherence of UPEC to uroepithelial cells in the human and murine urinary tracts where osmolality and pH vary. Previous work has shown that an acidic pH adversely affects the expression of type 1 pili. To determine if acid tolerance gene products may be regulating E. coli fim gene expression, a bank of K-12 strain acid tolerance gene mutants were screened using fimA-lux, fimB-lux, and fimE-lux fusions on single copy number plasmids. We have determined that a mutation in gadE increased transcription of all three fim genes, suggesting that GadE may be acting as a repressor in a low pH environment. Complementation of the gadE mutation restored fim gene transcription to wild-type levels. Moreover, mutations in gadX, gadW, crp, and cya also affected transcription of the three fim genes. To verify the role GadE plays in type 1 pilus expression, the NU149 gadE UPEC strain was tested. The gadE mutant had higher fimE gene transcript levels, a higher frequency of Phase-OFF positioning of fimS, and hemagglutination titres that were lower in strain NU149 gadE cultured in low pH medium as compared to the wild-type bacteria. The data demonstrate that UPEC fim genes are regulated directly or indirectly by the GadE protein and this could have some future bearing on the ability to prevent urinary tract infections by acidifying the urine and shutting off fim gene expression.

Balancing honesty and benevolence in dementia care: A commentary on therapeutic lies and codes of ethics.

AIM(S): This commentary suggests that within the context of dementia care, the revision of nursing codes of ethics to accommodate the acceptability of therapeutic lies under limited circumstances may be appropriate. BACKGROUND: Therapeutic lies (a prosocial lie) are told in the best interests of a person with dementia, to avoid distress or harm that may be derived from an act of truth-telling. However, their acceptability remains a contentious issue and is not reflected in nursing codes. EVALUATION: Nursing codes are reviewed in conjunction with empirical research on prosocial and therapeutic lies and how nurses interpret and implement codes. KEY ISSUES: Prosocial lies are perceived to be ethically preferable when truth-telling causes unnecessary harm. However, nurses may feel conflicted using therapeutic lies believing honesty to be obligatory. CONCLUSION: Codes may benefit from revision, by acknowledging the permissibility of therapeutic lies under limited circumstances. This may assist nurses with ethical decision-making and potentially reduce distress in this challenging area of practice. IMPLICATIONS FOR NURSING MANAGEMENT: It may be beneficial for nurse mangers to initiate discussions with staff regarding unnecessary harm and therapeutic lies. Nurse managers may also wish to advocate for the revision of codes as suggested in the commentary.

Enhanced fat suppression technique for breast imaging.

PURPOSE: To evaluate a new fat suppression technique using multiple fat suppression pulses intended for breast dynamic contrast-enhanced (DCE) imaging using segmented three-dimensional fast field echo (FFE). MATERIALS AND METHODS: The effect of multiple spectrally-selective fat suppression radiofrequency pulses was modeled using numerical Bloch-equation solutions for the following fat suppression techniques: spectral-selective inversion recovery (SPIR: one pulse), double fat suppression (DFS: two pulses, combining one SPIR pulse and one CHESS pulse), and triple fat suppression (TFS: three pulses, combining one SPIR pulse and two CHESS pulses). The simulation data were evaluated in terms of fat suppression performance, scan time, and specific absorption rate (SAR) relative to the SPIR technique. The DFS technique was selected as the optimal technique based on the efficacy of fat suppression versus the costs of scan time and SAR. The DFS technique was compared with SPIR in six volunteer studies using segmented T1 -weighted three-dimensional FFE. RESULTS: The DFS technique produced sufficient fat suppression using only two segments (two fat suppression shots). Breast DCE precontrast images using DFS presented uniform fat suppression compared with SPIR in both axial and sagittal scans in all six volunteers. CONCLUSION: DFS is a promising fat suppression technique for breast imaging even in regions with B1 (+) inhomogeneity.

Non-contrast enhanced MR angiography: physical principles.

Noncontrast-enhanced magnetic resonance angiography (NCE-MRA) methods have been demonstrated in anatomies throughout the body. Previously established NCE-MRA techniques suffered from long scan times or low sensitivity. Advances in hardware and software have made NCE-MRA scan times clinically feasible. Recent concerns over the safety of gadolinium-based contrast material combined with the expense of the material and its administration have generated a demand for NCE-MRA. In response, several new NCE-MRA methods have been developed. The physical mechanisms underlying five general classes of NCE-MRA methods (inflow effect, flow-dependency on cardiac phase, flow-encoding, spin labeling, and relaxation) are explained. The original techniques of time-of-flight (TOF) and phase contrast MRA (PC-MRA) are briefly introduced. New developments in NCE-MRA, including hybrid of opposite-contrast (HOP-MRA), four dimensional PC-MRA (4D Flow), cardiac-gated 3D fast-spin-echo, flow-sensitive dephasing (FSD), arterial spin labeling (ASL), and balanced steady-state free-precession (bSSFP) are highlighted. The primary applications, advantages, and limitations of established and emerging NCE-MRA techniques are discussed.

Spin-locked balanced steady-state free-precession (slSSFP).

A spin-locked balanced steady-state free-precession (slSSFP) pulse sequence is described that combines a balanced gradient-echo acquisition with an off-resonance spin-lock pulse for fast MRI. The transient and steady-state magnetization trajectory was solved numerically using the Bloch equations and was shown to be similar to balanced steady-state free-precession (bSSFP) for a range of T(2)/T(1) and flip angles, although the slSSFP steady-state could be maintained with considerably lower radio frequency (RF) power. In both simulations and brain scans performed at 7T, slSSFP was shown to exhibit similar contrast and signal-to-noise ratio (SNR) efficiency to bSSFP, but with significantly lower power.

Biomechanical and magnetic resonance characteristics of a cartilage-like equivalent generated in a suspension culture.

OBJECTIVE: To generate a cartilage biomaterial using a suspension culture with biophysical properties similar to native articular cartilage. DESIGN: A novel cartilage tissue equivalent (CTE) using a no-scaffold, high-density suspension culture of neonatal porcine chondrocytes was formed on poly 2-hydroxyethyl methacrylate-treated plates for up to 16 weeks. Equilibrium aggregate modulus and hydraulic permeability were measured at 8 and 16 weeks using confined compression stress relaxation experiments. The CTE proteoglycan composition was characterized using sodium and T(1rho) magnetic resonance imaging methods after 8 weeks. RESULTS: The resultant CTE produces a biomaterial consistent with a hyaline cartilage phenotype in appearance and expression of type II collagen and aggrecan. The equilibrium aggregate modulus and permeability for the 8-week specimens were 41.6 (standard deviation (SD) 4.3) kPa and 2.85(-13) (SD 2.45(-13)) m(4)/Ns, respectively, and, for the 16-week specimens, 35.2 (SD 7.6) kPa and 2.67(-13) (SD 1.06(-13)) m(4)/Ns, respectively. Average sodium concentration of the 8-week CTE ranged from 260 to 278 mM and average T(1rho) relaxation times from 105 to 107 ms, indicating proteoglycan content similar to that of native articular cartilage. CONCLUSION: The high-density culture method produced a CTE with characteristics that approach those of native articular cartilage. The CTE mechanical properties are similar to those of the native cartilage. The CTE developed in this study represents a promising methodological advancement in cartilage tissue engineering and cartilage repair.

Detection of changes in articular cartilage proteoglycan by T(1rho) magnetic resonance imaging.

The purpose of this work is to demonstrate the feasibility of T(1rho)-weighted magnetic resonance imaging (MRI) to quantitatively measure changes in proteoglycan content in cartilage. The T(1rho) MRI technique was implemented in an in vivo porcine animal model with rapidly induced cytokine-mediated cartilage degeneration. Six pigs were given an intra-articular injection of recombinant porcine interleukin-1beta (IL-1beta) into the knee joint before imaging to induce changes in cartilage via matrix metalloproteinase (MMP) induction. The induction of MMPs by IL-1 was used since it has been extensively studied in many systems and is known to create conditions that mimic in part characteristics similar to those of osteoarthritis. The contralateral knee joint was given a saline injection to serve as an internal control. T(1rho)-weighted MRI was performed on a 4 T whole-body clinical scanner employing a 2D fast spin-echo-based T(1rho) imaging sequence. T(1rho) relaxation parameter maps were computed from the T(1rho)-weighted image series. The average T(1rho) relaxation rate, R(1rho) (1/T(1rho)) of the IL-1beta-treated patellae was measured to be on average 25% lower than that of saline-injected patellae indicating a loss of proteoglycan. There was an average reduction of 49% in fixed charge density, measured via sodium MRI, of the IL-1beta-treated patellae relative to control corroborating the loss of proteoglycan. The effects of IL-1beta, primarily loss of PG, were confirmed by histological and immunochemical findings. The results from this study demonstrate that R(1rho) is able to track proteoglycan content in vivo.

T1rho-weighted MRI using a surface coil to transmit spin-lock pulses.

T1rho-weighted MRI is a novel basis for generating tissue contrast. However, it suffers from sensitivity to B1 inhomogeneity. First, excitation with a spatially varying B1 causes flip-angle artifacts and second, spin locking with an inhomogeneous B1 results in non-uniform T1rho contrast. In this study, we overcome the former complication with a specially designed spin-locking pulse sequence and we successfully obtain T1rho-weighted images with a surface coil. In this pulse sequence, the spin-lock pulse was divided into segments of equal duration and alternating phase. This "self-compensating" T1rho-preparatory pulse sequence was analyzed and the effect of an inhomogeneous B1 field was simulated using the Bloch equations. T1rho-weighted MR images of a phantom and a human knee joint in vivo were obtained on a clinical scanner with a surface coil to demonstrate the utility of the pulse sequence. The self-compensating T1rho-prepared pulses sequence resulted in substantially reduced image artifacts compared to the conventional, single-phase spin-lock pulse.

Automatic MR volume registration and its evaluation for the pelvis and prostate.

A three-dimensional (3D) mutual information registration method was created and used to register MRI volumes of the pelvis and prostate. It had special features to improve robustness. First, it used a multi-resolution approach and performed registration from low to high resolution. Second, it used two similarity measures, correlation coefficient at lower resolutions and mutual information at full resolution, because of their particular advantages. Third, we created a method to avoid local minima by restarting the registration with randomly perturbed parameters. The criterion for restarting was a correlation coefficient below an empirically determined threshold. Experiments determined the accuracy of registration under conditions found in potential applications in prostate cancer diagnosis, staging, treatment and interventional MRI (iMRI) guided therapies. Images were acquired in the diagnostic (supine) and treatment position (supine with legs raised). Images were also acquired as a function of bladder filling and the time interval between imaging sessions. Overall studies on three patients and three healthy volunteers, when both volumes in a pair were obtained in the diagnostic position under comparable conditions, bony landmarks and prostate 3D centroids were aligned within 1.6 +/- 0.2 mm and 1.4 +/- 0.2 mm, respectively, values only slightly larger than a voxel. Analysis suggests that actual errors are smaller because of the uncertainty in landmark localization and prostate segmentation. Between the diagnostic and treatment positions, bony landmarks continued to register well, but prostate centroids moved towards the posterior 2.8-3.4 mm. Manual cropping to remove voxels in the legs was necessary to register these images. In conclusion, automatic, rigid body registration is probably sufficiently accurate for many applications in prostate cancer. For potential iMRI-guided treatments, the small prostate displacement between the diagnostic and treatment positions can probably be avoided by acquiring volumes in similar positions and by reducing bladder and rectal volumes.

Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis.

RATIONALE AND OBJECTIVES: The aim of the study was to investigate the feasibility of using sodium magnetic resonance imaging (MRI) as a noninvasive quantitative technique for measuring proteoglycan (PG) content in an in vivo porcine model of osteoarthritis (OA). MATERIALS AND METHODS: Biochemical conditions similar to those of OA were created by an intra-articular injection of recombinant porcine interleukin-1beta (IL-1beta) into the knee joint of pigs (n = 6) before performing MRI. The contralateral knee joint was given a saline injection to serve as an internal control. Sodium MRI data were acquired on a 4-T clinical MR scanner and used to compute quantitative sodium and fixed charge density (FCD) maps based on a previously established methodology. In vivo FCD maps were compared with FCD maps obtained using ex vivo patellae harvested from the specimens. The tissue and joint fluid were subjected to histologic and immunohistochemical analyses as independent measurements of IL-1beta activity and PG loss. RESULTS: The average FCD of IL-1beta-treated patellae was measured to be 49% lower than that of saline-treated patellae, indicating a loss of PG content. These results were supported by histologic and immunochemical findings, most notably a reduction in staining for PG and an increase in matrix metalloproteinases in the synovial fluid. CONCLUSION: Sodium MRI can serve as a quantitative method to measure in vivo changes in PG content in an animal model of OA. The use of a noninvasive quantitative in vivo PG measurement technique such as sodium MRI on an animal model would aid greatly in efforts to monitor the efficacy of treatments for OA. Furthermore, these results indicate that early degenerative events could be detected noninvasively in vivo in humans with PG-depleting diseases such as OA.

3D-T1rho-relaxation mapping of articular cartilage: in vivo assessment of early degenerative changes in symptomatic osteoarthritic subjects.

RATIONALE AND OBJECTIVES: To determine the in vivo feasibility of quantifying early degenerative changes in patellofemoral joint of symptomatic human knee using spin-lattice relaxation time in the rotating frame (T(1rho)) magnetic resonance imaging (MRI). MATERIALS AND METHODS: All the MRI experiments were performed on a 1.5 T whole-body GE Signa clinical scanner using a custom built 15-cm diameter transmit-receive quadrature birdcage radiofrequency coil. The T(1rho)-prepared magnetization was imaged with a three-dimensional gradient-echo pulse sequence pre-encoded with a three-pulse cluster consisting of two hard 90 degrees pulses and a low power spin-lock pulse. Quantitative T(1rho) relaxation maps of asymptomatic (n = 8 males), and six symptomatic human volunteers (four men, two women) were computed using a appropriate signal expression. RESULTS: All six symptomatic volunteers showed elevation in T(1rho) relaxation times when compared with asymptomatic subjects. In symptomatic population, the T(1rho) relaxation times varied from 63 +/- 4 ms to 95 +/- 12 ms (mean +/- standard deviation) depending on the degree of cartilage degeneration. The increase in T(1rho) of symptomatic population was statistically significant (n = 6, P <.002) when compared with corresponding asymptomatic population. However, in asymptomatic population the relaxation times varied only from approximately 45 to 55 ms (n = 8, age range 22-45 years). CONCLUSION: Preliminary results demonstrated the in vivo feasibility of quantifying early biochemical changes in symptomatic osteoarthritis subjects employing T(1rho)-weighted MRI on a 1.5 T clinical scanner. This study on limited number of symptomatic population shows that T(1rho)-weighted MRI provides a noninvasive marker for quantitation of early degenerative changes of cartilage in vivo. However, further studies are needed to correlate early osteoarthritis determined from arthroscopy with T(1rho) in a large symptomatic population.

Cartilage volume quantification via Live Wire segmentation.

RATIONALE AND OBJECTIVES: A reduction in cartilage volume is characteristic of osteoarthritis and hence there exists a need for an accurate and reproducible method to measure in vivo cartilage volume. Quantification of cartilage volume from magnetic resonance (MR) images requires a segmentation technique such as the user-driven "Live Wire" strategy that can reliably delineate object volumes in a time-efficient manner. In the present work, the accuracy and reproducibility of the Live Wire method for the quantification of cartilage volume in MR images is evaluated. MATERIALS AND METHODS: The accuracy of the Live Wire method was assessed by comparing the MR-based volume measurement of a patellar cartilage-shaped phantom versus data calculated via water displacement. The inter- and intra-operator reproducibility of the technique was evaluated from Live Wire segmentation of the patellar cartilage volume from fat-suppressed 3-dimensional spoiled-gradient-echo images of five healthy human volunteers performed by three operators. To provide data for analysis of inter-scan reproducibility, the human scans were repeated five times with the aid of a leg-restraining jig to minimize repositioning error. RESULTS: The volume of the patellar cartilage-shaped phantom measured via Live Wire segmentation of MR images was within 97.8% of its true volume. The average inter- and intra-operator coefficients of variation of three operators were 3.0% and 0.4%, respectively. The average inter-scan coefficient of variation of five repeated scans of each volunteer was 2.7%. CONCLUSION: The data suggest that the Live Wire strategy is an accurate, reproducible, and efficient technique to measure cartilage volume in vivo in a feasible amount of operator time.

Noninvasive quantification of human nucleus pulposus pressure with use of T1rho-weighted magnetic resonance imaging.

BACKGROUND: Early diagnosis is a challenge in the treatment of degenerative disc disease. A noninvasive biomarker detecting functional mechanics of the disc is needed. T1rho-weighted imaging, a spin-lock magnetic resonance imaging technique, has shown promise for meeting this need in in vivo studies demonstrating the clinical feasibility of evaluating both intervertebral discs and articular cartilage. The objectives of the present study were (1) to quantitatively determine the relationship between T1rho relaxation time and measures of nucleus pulposus mechanics, and (2) to evaluate whether the quantitative relationship of T1rho relaxation time with the degenerative grade and glycosaminoglycan content extend to more severe degeneration. It was hypothesized that the isometric swelling pressure and compressive modulus would be directly correlated with the T1rho relaxation time and the apparent permeability would be inversely correlated with the T1rho relaxation time. METHODS: Eight cadaver human lumbar spines were imaged to measure T1rho relaxation times. The nucleus pulposus tissue from the L1 disc through the S1 disc was tested in confined compression to determine the swelling pressure, compressive modulus, and permeability. The glycosaminoglycan and water contents were measured in adjacent tissue. Linear regression analyses were performed to examine the correlation between the T1rho relaxation time and the other measured variables. Mechanical properties and biochemical content were evaluated for differences associated with degeneration. RESULTS: A positive linear correlation was observed between the T1rho relaxation time on the images of the nucleus pulposus and the swelling pressure (r = 0.59), glycosaminoglycan content per dry weight (r = 0.69), glycosaminoglycan per wet weight (r = 0.49), and water content (r = 0.53). No significant correlations were observed between the T1rho relaxation time and the modulus or permeability. Similarly, the T1rho relaxation time, swelling pressure, glycosaminoglycan content per dry weight, and water content were significantly altered with degeneration, whereas the modulus and permeability were not. CONCLUSIONS: T1rho-weighted magnetic resonance imaging has a strong potential as a quantitative biomarker of the mechanical function of the nucleus pulposus and of disc degeneration.

A pulse sequence for rapid in vivo spin-locked MRI.

PURPOSE: To develop a novel pulse sequence called spin-locked echo planar imaging (EPI), or (SLEPI), to perform rapid T1rho-weighted MRI. MATERIALS AND METHODS: SLEPI images were used to calculate T1rho maps in two healthy volunteers imaged on a 1.5-T Sonata Siemens MRI scanner. The head and extremity coils were used for imaging the brain and blood in the popliteal artery, respectively. RESULTS: SLEPI-measured T1rho was 83 msec and 103 msec in white (WM) and gray matter (GM), respectively, 584 msec in cerebrospinal fluid (CSF), and was similar to values obtained with the less time-efficient sequence based on a turbo spin-echo readout. T1rho was 183 msec in arterial blood at a spin-lock (SL) amplitude of 500 Hz. CONCLUSION: We demonstrate the feasibility of the SLEPI pulse sequence to perform rapid T1rho MRI. The sequence produced images of higher quality than a gradient-echo EPI sequence for the same contrast evolution times. We also discuss applications and limitations of the pulse sequence.

Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging.

STUDY DESIGN: T1rho relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. OBJECTIVE: To show the use of T1rho-weighted magnetic resonance imaging (MRI) for the assessment of degeneration and proteoglycan content in the human intervertebral disc. SUMMARY OF BACKGROUND DATA: Loss of proteoglycan in the nucleus pulposus occurs during early degeneration. Conventional MRI techniques cannot detect these early changes in the extracellular matrix content of the disc. T1rho MRI is sensitive to changes in proteoglycan content of articular cartilage and may, therefore, be sensitive to proteoglycan content in the intervertebral disc. METHODS: Intact human cadaveric lumbar spines were imaged on a clinical MR scanner. Average T1rho in the nucleus pulposus was calculated from quantitative T1rho maps. After MRI, the spines were dissected, and proteoglycan content of the nucleus pulposus was measured. Finally, the stage of degeneration was graded using conventional T2 images. RESULTS: T1rho decreased linearly with increasing degeneration (r = -0.76, P < 0.01) and age (r = -0.76, P < 0.01). Biochemical analysis revealed a strong linear correlation between T1rho and sulfated-glycosaminoglycan content. T1rho was moderately correlated with water content. CONCLUSIONS: Results from this study suggest that T1rho may provide a tool for the diagnosis of early degenerative changes in the disc. T1rho-weighted MRI is a noninvasive technique that may provide higher dynamic range than T2 and does not require a high static field or exogenous contrast agents.

In vivo measurement of plaque burden in a mouse model of Alzheimer's disease.

PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta (Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T1rho relaxation rate increases progressively with Alzheimer's disease (AD)-related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid precursor protein, and measured T1rho via quantitative relaxometric maps. RESULTS: A significant decrease in T1rho was observed in the cortex and hippocampus of 12- and 18-month-old animals compared to their age-matched controls. There was also a correlation between changes in T1rho and the age of the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for noninvasively determining AD-related pathology in APP/PS1 mice.

In vivo quantification of human lumbar disc degeneration using T(1rho)-weighted magnetic resonance imaging.

Diagnostic methods and biomarkers of early disc degeneration are needed as emerging treatment technologies develop (e.g., nucleus replacement, total disc arthroplasty, cell therapy, growth factor therapy) to serve as an alternative to lumbar spine fusion in treatment of low back pain. We have recently demonstrated in cadaveric human discs an MR imaging and analysis technique, spin-lock T(1rho)-weighted MRI, which may provide a quantitative, objective, and non-invasive assessment of disc degeneration. The goal of the present study was to assess the feasibility of using T(1rho) MRI in vivo to detect intervertebral disc degeneration. We evaluated ten asymptomatic 40-60-year-old subjects. Each subject was imaged on a 1.5 T whole-body clinical MR scanner. Mean T(1rho) values from a circular region of interest in the center of the nucleus pulposus were calculated from maps generated from a series of T(1rho)-weighted images. The degenerative grade of each lumbar disc was assessed from conventional T(2)-weighted images according to the Pfirmann classification system. The T(1rho) relaxation correlated significantly with disc degeneration (r=-0.51, P<0.01) and the values were consistent with our previous cadaveric study, in which we demonstrated correlation between T(1rho) and proteoglycan content. The technique allows for spatial measurements on a continuous rather than an integer-based scale, minimizes the potential for observer bias, has a greater dynamic range than T(2)-weighted imaging, and can be implemented on a 1.5 T clinical scanner without significant hardware modifications. Thus, there is a strong potential to use T(1rho) in vivo as a non-invasive biomarker of proteoglycan loss and early disc degeneration.

Quantification of cartilage biomechanical and biochemical properties via T1rho magnetic resonance imaging.

The aim of this study is to develop T1rho as an MR marker of the compositional and functional condition of cartilage. Specifically, we investigate the correlation of changes in cartilage biomechanical and biochemical properties with T1rho relaxation rate in a cytokine-induced model of degeneration. Bovine cartilage explants were cultured with 30 ng/mL of interleukin-1beta to mimic the cartilage degradation of early osteoarthritis. The average rate of T1rho relaxation was calculated from T(1rho) maps acquired on a 4.7 T research scanner. Stress-relaxation biomechanical tests were conducted with a confined compression apparatus to measure uniaxial aggregate modulus (HA) and hydraulic permeability (k0) using linear biphasic theory. Proteoglycan, collagen, and water content were measured via biochemical assays. Average T(1rho) relaxation rate was strongly correlated with proteoglycan content (R2 = 0.926), HA (R2 = 0.828), and log10 k0 (R2 = 0.862). Results of this study demonstrate that T1rho MRI can detect changes in proteoglycan content and biomechanical properties of cartilage in a physiologically relevant model of cartilage degeneration. The T1rho technique can potentially be used to noninvasively and quantitatively assess the biochemical and biomechanical characteristics of articular cartilage in humans during the progression of osteoarthritis.