Pseudotumors and High-Grade Aseptic Lymphocyte-Dominated Vasculitis-Associated Lesions Around Total Knee Replacements Identified at Aseptic Revision Surgery: Findings of a Large-Scale Histologic Review.

BACKGROUND: Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) development (including pseudotumors) secondary to metal debris generation around total hip arthroplasties is a well-recognized histopathologic phenomenon. Emerging data have highlighted a similar potential concern around TKAs although the body-of-knowledge has largely been limited to individual case reports or small retrospective case series. This study sought to establish the prevalence of pseudotumors or high-grade ALVALs seen at the revision of primary TKAs and to establish the correlation between histologic ALVAL grade and patient-reported functional outcome measures. METHODS: The findings of 321 non-infective (aseptic) patients undergoing unilateral revision knee surgery, at a high-volume tertiary referral center, were reviewed. Each case was independently histologically classified. Complete patient-reported functional outcome measures were available for 134 patients (42%) allowing correlation between functional performance and histopathology results. RESULTS: Five distinct pseudotumors and a further 18 high-grade ALVALs were histologically identified representing 1.6% and 5.6% of the cohort, respectively. When compared by histologic grade, Oxford Knee Score and Western Ontario and McMaster University's Osteoarthritis Index suggested a high correlation between ALVAL grade and functional knee scores. CONCLUSION: These findings suggest a prevalence of pseudotumors or high-grade ALVALs at revision TKA surgery of >7%. This unexpectedly high result may contribute insight into the previously under-appreciated significance of metal debris-related local tissue reactions around TKAs. The findings also demonstrate a strong near-linear inverse relationship between patient-reported clinical knee performance and the underlying histologic grade of local tissue reaction. These results have potential management implications for patients with underperforming TKAs and should prompt consideration of an ALVAL secondary to metallosis in the differential diagnosis. LEVEL OF EVIDENCE: This is a retrospective cohort study with Level III evidence.

Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs.

BACKGROUND: Once touted as the future of hip arthroplasty, metal-on-metal (MoM) bearing surfaces have fallen sharply from favor with the emergence of a strong body of evidence demonstrating unacceptably high premature implant failure rates. The previously unpredictable development of adverse local tissue reactions (ALTRs) has been a substantive contributor to this. Although the underlying pathophysiology of these so-called "pseudotumors" is now well understood, the fundamental predisposing patient risk factors have remained elusive. QUESTIONS/PURPOSES: The aim of this research, as a clinical-genotype correlation analysis, was to identify specific alleles (genes) associated with the development of ALTRs in patients with in situ MoM THAs. METHODS: A case-control study of patients who received a large-head, primary MoM THA between 2005 and 2008 was performed with a minimum followup of 5 years. Twenty-six patients who had undergone revision of a primary MoM THA secondary to symptomatic ALTRs were recruited. The mean timeframe from primary MoM THA to symptomatic revision was 5.5 years (range, 1-10 years). Twenty-eight control subjects were randomly selected asymptomatic patients with no evidence of ALTRs on protocol-specific screening. Baseline demographics and high-resolution genotype (human leukocyte antigen [HLA] Class II) were collected for all patients. Cohorts were similar with respect to age at the time of primary MoM THA (mean, 54.8 versus 54.9 years, p = 0.95) and serum cobalt (mean, 5.5 versus 8.5 µg/L, p = 0.09) and chromium concentrations (mean, 2.9 versus 4.2 µg/L, p = 0.27). The association between genotype and revision surgery secondary to ALTRs was determined with gender as a covariate. RESULTS: The prevalence of the risk genotype was 30% (16 of 54) among the entire cohort. Adjusting for sex, the odds of revision were 6.1 times greater among patients with the risk genotype present than among patients without (95% confidence interval [CI], 1.5-25.4; p = 0.01). Among females, the specificity of the risk genotype was 1.0 (95% CIexact, 0.5-1.0; pexact = 0.03), and for males, it was 0.8 (95% CIexact, 0.6-0.9; pexact < 0.01). CONCLUSIONS: The findings of this study suggest that, among patients with a primary MoM THA, allelic variation within the HLA Class II loci may be a strong, independent risk factor associated with the need for subsequent revision surgery secondary to pseudotumor formation. CLINICAL RELEVANCE: Given the hypothesis-generating nature of this novel undertaking, confirmatory prospective clinical studies are required to further elucidate this correlation and to explore the clinical utility of targeted genetic screening in this specific population. This research may, however, represent a key missing piece in the puzzle that is metal ion-induced pseudotumor formation.

Understanding immune-mediated cobalt/chromium allergy to orthopaedic implants: a meta-synthetic review.

BACKGROUND: The frequency of primary joint replacement surgery continues to increase worldwide. While largely considered biologically inert entities, an increasing body of evidence continues to validate a not insignificant incidence of allergic reactions to such implants. Little previous work has explored genuinely immune-mediated reactivity in this context. In the absence of a contemporary published summary on the topic, this paper explored the current state of understanding of cobalt/chromium allergy and proposes a patient management algorithm whereby such immune reactions are clinically suggested. METHODS: A structured, systematic literature review was performed by following PRISMA search principles to provide an updated review of this area. RESULTS: Thirty-six topic-related articles were identified, the majority reflecting lower tiers of scientific evidence with a lack of homogeneous quantitative data to facilitate valid cohort comparisons. Largely, the available literature represented small case series' or expert opinions. CONCLUSIONS: Despite increasing clinical awareness and acknowledgement of true allergy to joint replacement components, this review highlighted that the evidence base underpinning the diagnosis and management of such patients is limited. Both patient-reported metal allergy or skin patch testing are grossly unreliable methods and show almost no correlation with true immune reactivity. Recent studies suggested a potential role for patient-specific in vitro cellular activation testing and/or targeted genetic testing when cobalt/chromium allergy is clinically suspected. However, while likely representing the contemporary "best available" approaches both can be costly undertakings, are not yet universally available, and still require broader validation in non-research settings before wider uptake can be championed.

A role for artificial intelligence applications inside and outside of the operating theatre: a review of contemporary use associated with total knee arthroplasty.

BACKGROUND: Artificial intelligence (AI) has become involved in many aspects of everyday life, from voice-activated virtual assistants built into smartphones to global online search engines. Similarly, many areas of modern medicine have found ways to incorporate such technologies into mainstream practice. Despite the enthusiasm, robust evidence to support the utility of AI in contemporary total knee arthroplasty (TKA) remains limited. The purpose of this review was to provide an up-to-date summary of the use of AI in TKA and to explore its current and future value. METHODS: Initially, a structured systematic review of the literature was carried out, following PRISMA search principles, with the aim of summarising the understanding of the field and identifying clinical and knowledge gaps. RESULTS: A limited body of published work exists in this area. Much of the available literature is of poor methodological quality and many published studies could be best described as "demonstration of concepts" rather than "proof of concepts". There exists almost no independent validation of reported findings away from designer/host sites, and the extrapolation of key results to general orthopaedic sites is limited. CONCLUSION: While AI has certainly shown value in a small number of specific TKA-associated applications, the majority to date have focused on risk, cost and outcome prediction, rather than surgical care, per se. Extensive future work is needed to demonstrate external validity and reliability in non-designer settings. Well-performed studies are warranted to ensure that the scientific evidence base supporting the use of AI in knee arthroplasty matches the global hype.

Quantifying anterior pelvic roll during total hip arthroplasty in the lateral decubitus position.

BACKGROUND: Unintended pelvic positional change is an acknowledged intra-operative problem for hip arthroplasty, seen commonly with procedures performed in the lateral position. If unrecognised, such changes can dramatically alter final acetabular component anteversion potentially resulting in suboptimal construct performance. It has previously been suggested that pelvic roll of just 13° may be enough to place an otherwise perfectly orientated cup outside of conventional ± 10° safe zones. Using the real-time tracking capacity of a commercially available optical navigation system, we aimed to accurately quantify pelvic roll occurring during total hip arthroplasties (THAs) performed in the decubitus position. METHODS: Prospectively collected data for 107 consecutive, unilateral, THAs were interrogated to determine the magnitude of pelvic movement around a central longitudinal axis (i.e. AP roll). Correlation statistics with patient age and body mass index (BMI) were also calculated. RESULTS: A mean pelvic roll of 9.5° was observed, being anterior in 96% of cases. Of these, 18.3% of hips had a magnitude of roll greater than 13°. There were no statistically significant independent correlations observed between age (p = 0.87) or BMI (p = 0.59) and mean roll. CONCLUSIONS: Errors in achieving acetabular target version may result in numerous post-operative concerns including instability/dislocation, bearing wear, squeaking, range-of-movement limitation and increased revision rate. In a general cohort, our findings suggest a mean anterior pelvic roll during THA of nearly 10°. Without purposeful correction, this may cause substantial deviation from intended target positions. Future work is indicated to map changing pelvic roll during THA which is likely to follow a nonlinear trajectory. Level of evidence: IV. .

Corrigendum to "Early Revision Rates of Total Hip Arthroplasty Using the Intellijoint HIP Computer Navigation System: A Study From the Australian National Joint Replacement Registry of 1911 Procedures." [Arthroplasty Today 18 (2022) 149-156].

[This corrects the article DOI: 10.1016/j.artd.2022.09.019.].

Identification of protective and 'at risk' HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings.

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. 'Controls' were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two 'at risk' alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.

Clinical Impact of Pelvic Malrotation on Radiograph-Based Preoperative Planning for Total Hip Arthroplasty: A Proof-of-Concept and Prudent Prediction of Acceptable Rotation.

Introduction: Pelvic rotation (PR) on preoperative radiograph templating can affect various critical measured acetabular angles and potentially outcomes of successful total hip arthroplasty (THA). Optimising anatomical reconstruction of the joint is essential to achieve function, longevity and prevention of complications following surgery. There is limited literature that standardises the degree of acceptable PR on radiograph or its effects on the fitting of acetabular prostheses. Objective: This study aimed to develop a proof-of-concept that quantifies how PR can affect various acetabular angles used in pre-operative THA templating and to formulate a practicable method of determining if the preoperative PR is acceptable. Materials and methods: Computerised tomography (CT) models from three control and two THA patients were generated and manipulated in various degrees of PR. CT slices were thickened to simulate radiographs and acetabular angles measured. Results: The acetabular anteversion distance (AAD) and lateral opening angle (LOA) demonstrated a linear and quadratic relationship with good correlation (R 2 = 0.923, R 2 = 0.710 respectively, p < 0.0001) in relation to PR. Change in area of prosthesis (AOP) demonstrated a good linear correlation (r 2 = 0.774 and r 2 = 0.875, p < 0.0001) with PR. Two novel measurements were used to estimate the degree of PR from a pelvic radiograph; the horizontal distance between pubic symphysis and middle of sacrococcygeal joint (PSSC) and the simplified pelvic rotation ratio (SPRR). A strong correlation between PSSC and SPRR with change in PR was observed (R 2 = 0.970, R 2 = 0.953, p < 0.001). Conclusion: Preliminary result suggests that an SPRR > 2.0 correlates to PR > 20° with potential to have a clinical impact on preoperative measurements.

Artificial intelligence in orthopedic surgery: evolution, current state and future directions.

Technological advances continue to evolve at a breath-taking pace. Computer-navigation, robot-assistance and three-dimensional digital planning have become commonplace in many parts of the world. With near exponential advances in computer processing capacity, and the advent, progressive understanding and refinement of software algorithms, medicine and orthopaedic surgery have begun to delve into artificial intelligence (AI) systems. While for some, such applications still seem in the realm of science fiction, these technologies are already in selective clinical use and are likely to soon see wider uptake. The purpose of this structured review was to provide an understandable summary to non-academic orthopaedic surgeons, exploring key definitions and basic development principles of AI technology as it currently stands. To ensure content validity and representativeness, a structured, systematic review was performed following the accepted PRISMA principles. The paper concludes with a forward-look into heralded and potential applications of AI technology in orthopedic surgery.While not intended to be a detailed technical description of the complex processing that underpins AI applications, this work will take a small step forward in demystifying some of the commonly-held misconceptions regarding AI and its potential benefits to patients and surgeons. With evidence-supported broader awareness, we aim to foster an open-mindedness among clinicians toward such technologies in the future.

Patellar button compatibility in the conversion of Patellofemoral Arthroplasty to a Total Knee Arthroplasty: A review of the contemporary literature.

BACKGROUND: Compared to total knee arthroplasty (TKA), patellofemoral arthroplasty (PFA) is a far less commonly performed operation. However, in carefully selected cohorts, PFA continues to be an appropriate treatment option for end-stage isolated patellofemoral joint osteoarthritis. In the later situation whereby a PFA is considered for conversion to a TKA - often due to disease progression - uncertainty remains regarding optimal management of the in situ patellar button. This review of the contemporary literature aimed to provide a summary of the current evidence to support surgeon decision-making, by evaluating the compatibility, efficacy, and survivorship of retained versus revised patellar buttons in PFA-to-TKA conversion. Specific focus was paid to implant design and technical considerations during revision, plus post-operative patient-reported outcomes and modes of secondary patellar component failure. METHODS: A review of the Embase, Cochrane and PubMed databases was performed following PRISMA search principles. RESULTS: This investigation highlights that the fate of patellar buttons in PFA-to-TKA conversion has previously been poorly studied, with scant publication data available. Most reports have been of singular cases or small cohort series. Larger formal RCTs and level 1 evidence are lacking. CONCLUSION: The findings herein suggest that surgeons can confidently retain well-fixed, undamaged, dome-shaped all-polyethylene patellar buttons in the conversion of a PFA to TKA with the expectation of acceptable mid-term performance and survivorship, as long as congruent tracking with the new tibiofemoral components is achieved. This result is likely translatable to the majority of contemporary, all-polyethylene, dome-shaped patellar buttons, even with manufacturer mismatch.

Early Revision Rates of Total Hip Arthroplasty Using the Intellijoint HIP Computer Navigation System: A Study From the Australian National Joint Replacement Registry of 1911 Procedures.

Background: Total hip arthroplasty (THA) is an effective treatment for symptomatic hip osteoarthritis. The aim of this study was to determine the revision outcome of commercially available navigation technologies. Methods: Data from the Australian Orthopaedic Association National Joint Replacement Registry from January 2016 to December 2020 included all primary THA procedures performed for osteoarthritis. Procedures using the Intellijoint HIP navigation system were identified and compared to procedures using "other" computer navigation systems and to nonnavigated procedures. The cumulative percent revision (CPR) was compared between the 3 groups using Kaplan-Meier estimates of survivorship and hazard ratios from Cox proportional hazards models, adjusted for age and gender. Results: There were 1911 procedures that used the Intellijoint system, 4081 used "other" computer navigation systems, and 160,661 were nonnavigated procedures. The all-cause 2-year CPR rate for the Intellijoint system was 1.8% (95% confidence interval [CI], 1.2-2.6), compared to 2.2% (95% CI, 1.8-2.8) for other navigated cases and 2.2% (95% CI, 2.1-2.3) for nonnavigated cases. A prosthesis analysis identified the Paragon/Acetabular Shell THAs combined with the Intellijoint system to have a higher (3.4%) rate of revision than nonnavigated THAs (hazard ratio = 2.00 [95% CI, 1.01-4.00], P = .048). When this combination was excluded, the Intellijoint group demonstrated a 2-year CPR of 1.3%. There was no statistical difference in the CPR between the 3 groups before or after excluding the Paragon/Acetabular Shell system. Conclusions: The preliminary data presented demonstrate no statistical difference in all-cause revision rates when comparing the Intellijoint system with "other" navigation systems and "nonnavigated" approaches for primary THAs. Level of evidence: III (National registry analysis).

In vitro evaluation of a manganese chloride phantom-based MRI technique for quantitative determination of lumbar intervertebral disc composition and condition.

The application of MRI as a non-invasive, quantitative tool for diagnosing lumbar intervertebral disc degeneration is currently an area of active research. The objective of this study was to examine, in vitro, the efficacy of a manganese chloride phantom-based MRI technique for quantitatively assessing lumbar disc composition and degenerative condition. Sixteen human lumbar discs were imaged ex vivo using T2-weighted MRI, and assigned a quantitative grade based on the relative signal intensities of nine phantoms containing serial concentrations of manganese chloride. Discs were then graded macroscopically for degenerative condition, and water and uronic acid (glycosaminoglycan) contents were determined. MRI ranking exhibited significant and strong negative correlation with nucleus pulposus uronic acid content (r = -0.78). MRI grades were significantly higher for degenerate discs. The technique described presents immediate potential for in vitro studies requiring robust, minimally invasive and quantitative determination of lumbar disc composition and condition. Additionally, the technique may have potential as a clinical tool for diagnosing lumbar disc degeneration as it provides a standardised series of reference phantoms facilitating cross-platform consistency, requires short scan times and simple T2-weighted signal intensity measurements.

Eradicating Fungal Periprosthetic TKA "Super-infection": Review of the Contemporary Literature and Consideration of Antibiotic-Impregnated Dissolving Calcium Sulfate Beads as a Novel PJI Treatment Adjunct.

Fungal periprosthetic joint infections are an uncommon but potentially devastating complication of arthroplasty surgery. The concurrent presence of a coexistent bacterial pathogen-a so called "super-infection"-adds further complexity. With delays to definitive diagnosis and a large number of procedures before cure, the associated physical and psychological morbidity is considerable. Beyond this, the economic and resource burden can be substantial. This case report presents the successful rapid treatment of an atypical bacterial and fungal periprosthetic super-infection with two-stage revision surgery augmented with a commercially available dissolving calcium sulfate bead system permitting targeted local antifungal elution. While not the panacea for treatment, these beads provide another potentially useful tool in the atypical pathogen eradication armamentarium. Much research is still indicated to define the optimal care pathway for fungal periprosthetic super-infections.

Gabapentoids in knee replacement surgery: contemporary, multi-modal, peri-operative analgesia.

Pain remains a significant barrier to rapid patient recovery and rehabilitation post-surgery, particularly after joint replacement surgery. Historically, protocols used for peri-operative pain management have been largely reactive and dependent on opioid use, with adjunctive non-steroidal and other simple analgesia. This review explores the evidence supporting the use of gabapentoids (eg. Lyrica®) in surgical fields, then in orthopaedics more specifically, and finally in the targeted domain of total knee replacement (TKR) surgery. The concept of 'pre-emptive' analgesia is also explored. Gabapentoids have shown clinical value in reducing the patient-reported pain experience and also decreasing concurrent opioid requirements in the post-surgical period in a number of surgical areas, however there remains no consensus for their optimal use in patients undergoing knee arthroplasty. Reported adverse effects including sedation and potential respiratory depression should herald some caution, and monitored use in 'at risk' patient groups. There have been a small number of clinical trials conducted around the use of gabapentoids in TKR, however the validity and generalisability of these results have been limited by small sample sizes, and cross-study analysis is confounded by adoption of inconsistent analgesic protocols, non-comparable dosing regimes, poor (or absent) control selection, and cohort heterogeneity. High-quality trials are needed to allow the role of gabapentoids in multi-modal peri-operative analgesic pathways to be better defined, to permit wider endorsement for main-stream or standardised care.

Determining disk hydration status with a MnCl2-based MR model.

PURPOSE: An extensive body of literature demonstrates a strong correlation between intervertebral disk (IVD) hydration status (HS) and functional spinal integrity. However, to date, in vivo IVD HS assessment has relied largely on subjective and nonrepeatable measures. The aim of this study was to establish the consistency of signal homogeneity of a novel semisolid-state manganese chloride (MnCl2)-based phantom for HS correlation using conventional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Sixteen MnCl2 phantoms, of increasing relative molar concentration (range 0.01 to 2.9 mM), underwent axial MR imaging. Phantom signal-to-noise ratio measures were recorded for each concentration on several sequence types. Coefficient of variance data were calculated to determine the degree of MR signal variation at each concentration. RESULTS: Analysis of variance testing suggested no significant difference in coefficient of variance data derived from phantom signal intensities using either T1- (P = .13) or T2-weighted sequence types (P = .96), suggesting a high degree of relative signal homogeneity. CONCLUSIONS: The findings of this study suggest that a MnCl2 phantom combined with a nonfield reactive, semirigid, gelatin suspension media can produce a predictable, concentration-related, homogeneous MR signal response. This may be an appropriate base material for a noninvasive model to allow accurate quantification of the hydration status of the in vivo human IVD.

Occupationally-acquired noise-induced hearing loss: a senseless workplace hazard.

OBJECTIVES: Occupational noise-induced hearing loss (ONIHL) describes an acquired hearing deficiency directly attributable to excessive workplace noise exposure. Data suggest that excessive noise attributes to approximately 37% of all adult causes of hearing loss and remains a significant contributor to employment-related morbidity internationally. Typically insidiously-acquired, often without frank progressive symptomatology, regional medical agencies continue to struggle with this potentially debilitating condition. The aim of the study was to provide a synopsis of the current understanding of ONIHL, its impact on individual workers and the wider international community, and to identify barriers to more uniform adoption of personal hearing protection. MATERIALS AND METHODS: A review of the contemporary literature was performed using defined keyword searches and OVID, PubMed, and Google Scholar as primary electronic search engines. RESULTS: A number of published works were identified, describing aspects of the relationship between workplace-related noise exposure and subsequent development of employee hearing impairment, which demonstrate an overwhelming gender imbalance, with up to 97% of affected individuals being male. Industry-specific associations (e.g., mining, manufacturing and heavy construction) were well documented, as were links to toxin-specific exposures, in the recognized development of hearing loss. However, evidence of integration of appraisal of the topically-current area of genetic susceptibility was often lacking. Much discordance still exists among international agencies in the prescriptive regulation and enforcement of "safe" exposure limits. CONCLUSIONS: Despite a high level of public awareness regarding the importance of hearing preservation and increasingly stringent international occupational health, safety and welfare requirements mandating provision of safer work environments, ONIHL continues to be a significant occupational hazard. ONIHL is permanent and may cause significant disability, for which there currently exists no cure, but is largely overtly-preventable. The impact of ONIHL on the global transition toward dominant communication-rich white-collar employment roles is difficult to quantitate, but is likely to be substantive upon the afflicted individual. In the mainstream setting, exposure-avoidance strategies aimed to reduce the incidence of ONIHL remain the focus of public health and occupational medicine approaches.

A MnCl2-based MR signal intensity linear response phantom.

PURPOSE: This study aimed to develop a manganese chloride (MnCl2)-based phantom model that would allow progressive quantitative assessment of tissue hydration based on observed magnetic resonance (MR) imaging signal intensity (SI) linearity characteristics. MATERIALS AND METHODS: The study was performed using a progressive signal refinement technique that allowed development of an imaging tool for semiquantitative sequential discrimination of MR signal responses. A series of 82 phantoms comprising a gelatin-set MnCl2 composite were imaged under basic T1- and T2-weighted conditions. MR SI measurements were taken using region-of-interest selection, and MnCl2 concentrations were adjusted to allow development of a pair of 8-tube phantoms. These phantoms permitted progressive incremental assessment of hydration based on fundamental MR SI response. RESULTS: Statistical analysis showed that phantom MR signal response linearity can be achieved using the phantoms described under both T1 and T2 imaging conditions, yielding R2 values of 0.97 and 0.94, respectively. CONCLUSION: This novel MnCl2-based phantom can be used as a noninvasive reference standard for quantitative classification of in vivo tissue hydration based on routine clinical MR imaging sequences. Progressive correlation testing using a human cartilage sample should be performed to further refine the model for clinical application.