Regional anaesthesia training in the UK - a national survey.

Background: Adequate training of anaesthetists in regional anaesthesia is important to ensure optimal patient access to regional anaesthesia. Methods: We undertook a national survey of UK trainee anaesthetists and Royal College of Anaesthetists (RCoA) tutors to assess experiences of training in regional anaesthesia. We performed descriptive statistics for baseline characteristics, and logistic regression of training indices and tutor confidence that their hospital could provide regional anaesthesia training at all three stages of the RCoA 2021 curriculum. Results: A total of 492 trainees (19.2%) and 114 tutors (45.2%) completed the survey. Trainees were less likely to have received training in chest/abdominal wall compared with upper/lower limb blocks {erector spinae vs femoral block (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.16-0.39), P<0.001}, or achieved >20 chest/abdominal wall blocks by Stage 3 of training (chest vs lower limb block [OR 0.09, 95% CI 0.05-0.15, P<0.001]. There was a strong association between training received, number of blocks performed (>20 vs 0-5 blocks), and self-reported ability to perform blocks independently, OR 20.9 (95% CI 9.38-53.2). 24/182 (13%) and 10/182 (5.5%) of trainees had performed ≥50 non-obstetric lumbar and thoracic epidurals, respectively, by Stage 3 training. There was a positive association between having a lead clinician for regional anaesthesia, particularly those with paid sessions, and reported confidence to provide regional anaesthesia training at all stages of the curriculum (Stage 3 OR 7.27 [95% CI 2.64-22.0]). Conclusion: Our results confirm the importance of clinical experience and access to training in regional anaesthesia, and support the introduction of departmental regional anaesthesia leads to improve equity and quality in training opportunities.

Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of upper and lower limb nerve blocks.

BACKGROUND: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. METHODS: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. RESULTS: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. CONCLUSIONS: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.

Augmented Reality in Ultrasound-Guided Regional Anaesthesia: An Exploratory Study on Models With Potential Implications for Training.

Introduction Needle tip visualisation is a key skill required for the safe practice of ultrasound-guided regional anaesthesia (UGRA). This exploratory study assesses the utility of a novel augmented reality device, NeedleTrainer™, to differentiate between anaesthetists with varying levels of UGRA experience in a simulated environment. Methods Four groups of five participants were recruited (n = 20): novice, early career, experienced anaesthetists, and UGRA experts. Each participant performed three simulated UGRA blocks using NeedleTrainer™ on healthy volunteers (n = 60). The primary aim was to determine whether there was a difference in needle tip visibility, as calculated by the device, between groups of anaesthetists with differing levels of UGRA experience. Secondary aims included the assessment of simulated block conduct by an expert assessor and subjective participant self-assessment. Results The percentage of time the simulated needle tip was maintained in view was higher in the UGRA expert group (57.1%) versus the other three groups (novice 41.8%, early career 44.5%, and experienced anaesthetists 43.6%), but did not reach statistical significance (p = 0.05). An expert assessor was able to differentiate between participants of different UGRA experience when assessing needle tip visibility (novice 3.3 out of 10, early career 5.1, experienced anaesthetists 5.9, UGRA expert group 8.7; p < 0.01) and final needle tip placement (novice 4.2 out of 10, early career 5.6, experienced anaesthetists 6.8, UGRA expert group 8.9; p < 0.01). Subjective self-assessment by participants did not differentiate UGRA experience when assessing needle tip visibility (p = 0.07) or final needle tip placement (p = 0.07). Discussion An expert assessor was able to differentiate between participants with different levels of UGRA experience in this simulated environment. Objective NeedleTrainer™ and subjective participant assessments did not reach statistical significance. The findings are novel as simulated needling using live human subjects has not been assessed before, and no previous studies have attempted to objectively quantify needle tip visibility during simulated UGRA techniques. Future research should include larger sample sizes to further assess the potential use of such technology.

Pilot Study Exploring if an Augmented Reality NeedleTrainer Device Improves Novice Performance of a Simulated Central Venous Catheter Insertion on a Phantom.

Introduction Needle insertion and visualisation skills needed for ultrasound (US)-guided procedures can be challenging to acquire. The novel NeedleTrainer device superimposes a digital holographic needle on a real-time US image display without puncturing a surface. The aim of this randomised control study was to compare the success of trainees performing a simulated central venous catheter insertion on a phantom either with or without prior NeedleTrainer device practice. Methods West of Scotland junior trainees who had not performed insertion of a central venous catheter were randomised into two groups (n=20). Participants undertook standardized online training through a pre-recorded video and training on how to handle a US probe. Group 1 had 10 minutes of supervised training with the NeedleTrainer device. Group 2 were a control group. Participants were assessed on needle insertion to a pre-defined target vein in a phantom. The outcome measures were the time taken for needle placement (secs), number of needle passes (n), operator confidence (0-10), assessor confidence (0-10), and NASA task load index score. Results The mean mental demand score in the control group was 7.65 (SD 3.5) compared to 12.8 (SD 2.2, p=0.005) in the NeedleTrainer group. There was no statistical difference between the groups in any of the other outcome measures. Discussion This was a small pilot study, and small participant numbers may have impacted the statistical significance. There is natural variation of skill within participants that could not have been controlled for. The difference in pressure needed using the NeedleTrainer compared to a real needle may impact the outcome measures.

Evaluation of the impact of assistive artificial intelligence on ultrasound scanning for regional anaesthesia.

BACKGROUND: Ultrasound-guided regional anaesthesia relies on the visualisation of key landmark, target, and safety structures on ultrasound. However, this can be challenging, particularly for inexperienced practitioners. Artificial intelligence (AI) is increasingly being applied to medical image interpretation, including ultrasound. In this exploratory study, we evaluated ultrasound scanning performance by non-experts in ultrasound-guided regional anaesthesia, with and without the use of an assistive AI device. METHODS: Twenty-one anaesthetists, all non-experts in ultrasound-guided regional anaesthesia, underwent a standardised teaching session in ultrasound scanning for six peripheral nerve blocks. All then performed a scan for each block; half of the scans were performed with AI assistance and half without. Experts assessed acquisition of the correct block view and correct identification of sono-anatomical structures on each view. Participants reported scan confidence, experts provided a global rating score of scan performance, and scans were timed. RESULTS: Experts assessed 126 ultrasound scans. Participants acquired the correct block view in 56/62 (90.3%) scans with the device compared with 47/62 (75.1%) without (P=0.031, two data points lost). Correct identification of sono-anatomical structures on the view was 188/212 (88.8%) with the device compared with 161/208 (77.4%) without (P=0.002). There was no significant overall difference in participant confidence, expert global performance score, or scan time. CONCLUSIONS: Use of an assistive AI device was associated with improved ultrasound image acquisition and interpretation. Such technology holds potential to augment performance of ultrasound scanning for regional anaesthesia by non-experts, potentially expanding patient access to these techniques. CLINICAL TRIAL REGISTRATION: NCT05156099.

Assistive artificial intelligence for ultrasound image interpretation in regional anaesthesia: an external validation study.

BACKGROUND: Ultrasonound is used to identify anatomical structures during regional anaesthesia and to guide needle insertion and injection of local anaesthetic. ScanNav Anatomy Peripheral Nerve Block (Intelligent Ultrasound, Cardiff, UK) is an artificial intelligence-based device that produces a colour overlay on real-time B-mode ultrasound to highlight anatomical structures of interest. We evaluated the accuracy of the artificial-intelligence colour overlay and its perceived influence on risk of adverse events or block failure. METHODS: Ultrasound-guided regional anaesthesia experts acquired 720 videos from 40 volunteers (across nine anatomical regions) without using the device. The artificial-intelligence colour overlay was subsequently applied. Three more experts independently reviewed each video (with the original unmodified video) to assess accuracy of the colour overlay in relation to key anatomical structures (true positive/negative and false positive/negative) and the potential for highlighting to modify perceived risk of adverse events (needle trauma to nerves, arteries, pleura, and peritoneum) or block failure. RESULTS: The artificial-intelligence models identified the structure of interest in 93.5% of cases (1519/1624), with a false-negative rate of 3.0% (48/1624) and a false-positive rate of 3.5% (57/1624). Highlighting was judged to reduce the risk of unwanted needle trauma to nerves, arteries, pleura, and peritoneum in 62.9-86.4% of cases (302/480 to 345/400), and to increase the risk in 0.0-1.7% (0/160 to 8/480). Risk of block failure was reported to be reduced in 81.3% of scans (585/720) and to be increased in 1.8% (13/720). CONCLUSIONS: Artificial intelligence-based devices can potentially aid image acquisition and interpretation in ultrasound-guided regional anaesthesia. Further studies are necessary to demonstrate their effectiveness in supporting training and clinical practice. CLINICAL TRIAL REGISTRATION: NCT04906018.

Recommendations for anatomical structures to identify on ultrasound for the performance of intermediate and advanced blocks in ultrasound-guided regional anesthesia.

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for "block view" (which visualizes the block site and is maintained for needle insertion/injection). A "strong recommendation" was made if ≥75% of participants rated any structure as "definitely include" in any round. A "weak recommendation" was made if >50% of participants rated it as "definitely include" or "probably include" for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a "strong recommendation" was made for 60 structures on orientation scanning and 44 on the block view. A "weak recommendation" was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Artificial Intelligence: Innovation to Assist in the Identification of Sono-anatomy for Ultrasound-Guided Regional Anaesthesia.

Ultrasound-guided regional anaesthesia (UGRA) involves the targeted deposition of local anaesthesia to inhibit the function of peripheral nerves. Ultrasound allows the visualisation of nerves and the surrounding structures, to guide needle insertion to a perineural or fascial plane end point for injection. However, it is challenging to develop the necessary skills to acquire and interpret optimal ultrasound images. Sound anatomical knowledge is required and human image analysis is fallible, limited by heuristic behaviours and fatigue, while its subjectivity leads to varied interpretation even amongst experts. Therefore, to maximise the potential benefit of ultrasound guidance, innovation in sono-anatomical identification is required.Artificial intelligence (AI) is rapidly infiltrating many aspects of everyday life. Advances related to medicine have been slower, in part because of the regulatory approval process needing to thoroughly evaluate the risk-benefit ratio of new devices. One area of AI to show significant promise is computer vision (a branch of AI dealing with how computers interpret the visual world), which is particularly relevant to medical image interpretation. AI includes the subfields of machine learning and deep learning, techniques used to interpret or label images. Deep learning systems may hold potential to support ultrasound image interpretation in UGRA but must be trained and validated on data prior to clinical use.Review of the current UGRA literature compares the success and generalisability of deep learning and non-deep learning approaches to image segmentation and explains how computers are able to track structures such as nerves through image frames. We conclude this review with a case study from industry (ScanNav Anatomy Peripheral Nerve Block; Intelligent Ultrasound Limited). This includes a more detailed discussion of the AI approach involved in this system and reviews current evidence of the system performance.The authors discuss how this technology may be best used to assist anaesthetists and what effects this may have on the future of learning and practice of UGRA. Finally, we discuss possible avenues for AI within UGRA and the associated implications.

Exploring the utility of assistive artificial intelligence for ultrasound scanning in regional anesthesia.

INTRODUCTION: Ultrasound-guided regional anesthesia (UGRA) involves the acquisition and interpretation of ultrasound images to delineate sonoanatomy. This study explores the utility of a novel artificial intelligence (AI) device designed to assist in this task (ScanNav Anatomy Peripheral Nerve Block; ScanNav), which applies a color overlay on real-time ultrasound to highlight key anatomical structures. METHODS: Thirty anesthesiologists, 15 non-experts and 15 experts in UGRA, performed 240 ultrasound scans across nine peripheral nerve block regions. Half were performed with ScanNav. After scanning each block region, participants completed a questionnaire on the utility of the device in relation to training, teaching, and clinical practice in ultrasound scanning for UGRA. Ultrasound and color overlay output were recorded from scans performed with ScanNav. Experts present during the scans (real-time experts) were asked to assess potential for increased risk associated with use of the device (eg, needle trauma to safety structures). This was compared with experts who viewed the AI scans remotely. RESULTS: Non-experts were more likely to provide positive and less likely to provide negative feedback than experts (p=0.001). Positive feedback was provided most frequently by non-experts on the potential role for training (37/60, 61.7%); for experts, it was for its utility in teaching (30/60, 50%). Real-time and remote experts reported a potentially increased risk in 12/254 (4.7%) vs 8/254 (3.1%, p=0.362) scans, respectively. DISCUSSION: ScanNav shows potential to support non-experts in training and clinical practice, and experts in teaching UGRA. Such technology may aid the uptake and generalizability of UGRA. TRIAL REGISTRATION NUMBER: NCT04918693.

International consensus on anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia.

There is no universally agreed set of anatomical structures that must be identified on ultrasound for the performance of ultrasound-guided regional anesthesia (UGRA) techniques. This study aimed to produce standardized recommendations for core (minimum) structures to identify during seven basic blocks. An international consensus was sought through a modified Delphi process. A long-list of anatomical structures was refined through serial review by key opinion leaders in UGRA. All rounds were conducted remotely and anonymously to facilitate equal contribution of each participant. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for the "block view" (which visualizes the block site and is maintained for needle insertion/injection). Strong recommendations for inclusion were made if ≥75% of participants rated a structure as "definitely include" in any round. Weak recommendations were made if >50% of participants rated a structure as "definitely include" or "probably include" for all rounds (but the criterion for "strong recommendation" was never met). Thirty-six participants (94.7%) completed all rounds. 128 structures were reviewed; a "strong recommendation" is made for 35 structures on orientation scanning and 28 for the block view. A "weak recommendation" is made for 36 and 20 structures, respectively. This study provides recommendations on the core (minimum) set of anatomical structures to identify during ultrasound scanning for seven basic blocks in UGRA. They are intended to support consistent practice, empower non-experts using basic UGRA techniques, and standardize teaching and research.

Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of abdominal wall, paraspinal, and chest wall blocks.

BACKGROUND: There is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques. METHODS: We conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement. RESULTS: Sixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified. CONCLUSIONS: Harmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.

Identifying anatomical structures on ultrasound: assistive artificial intelligence in ultrasound-guided regional anesthesia.

Ultrasound-guided regional anesthesia involves visualizing sono-anatomy to guide needle insertion and the perineural injection of local anesthetic. Anatomical knowledge and recognition of anatomical structures on ultrasound are known to be imperfect amongst anesthesiologists. This investigation evaluates the performance of an assistive artificial intelligence (AI) system in aiding the identification of anatomical structures on ultrasound. Three independent experts in regional anesthesia reviewed 40 ultrasound scans of seven body regions. Unmodified ultrasound videos were presented side-by-side with AI-highlighted ultrasound videos. Experts rated the overall system performance, ascertained whether highlighting helped identify specific anatomical structures, and provided opinion on whether it would help confirm the correct ultrasound view to a less experienced practitioner. Two hundred and seventy-five assessments were performed (five videos contained inadequate views); mean highlighting scores ranged from 7.87 to 8.69 (out of 10). The Kruskal-Wallis H-test showed a statistically significant difference in the overall performance rating (χ2 [6] = 36.719, asymptotic p < 0.001); regions containing a prominent vascular landmark ranked most highly. AI-highlighting was helpful in identifying specific anatomical structures in 1330/1334 cases (99.7%) and for confirming the correct ultrasound view in 273/275 scans (99.3%). These data demonstrate the clinical utility of an assistive AI system in aiding the identification of anatomical structures on ultrasound during ultrasound-guided regional anesthesia. Whilst further evaluation must follow, such technology may present an opportunity to enhance clinical practice and energize the important field of clinical anatomy amongst clinicians.

'Golden Patient': A quality improvement project aiming to improve trauma theatre efficiency in the Royal Gwent Hospital.

The efficiency of trauma lists when compared with elective orthopaedic lists is a frustration of many orthopaedic departments. At the Royal Gwent Hospital, late start times affecting total operating capacity of the trauma list were recognised as a problem within the department. The design team aimed to improve the start time of the list with the introduction of the 'golden patient' initiative. A protocol was agreed between the orthopaedic, anaesthetic and theatre staff where a 'golden patient' was selected for preoperative anaesthetic assessment by 14:00 the day before surgery and sent for at 08:15 as the first case on the trauma list. Baseline data was collected over a month. Two Plan-Do-Study-Act (PDSA) cycles were completed, one on the month the 'golden patient' initiative was implemented and one 4 months after the change. All data was collected from the Operating Room Management Information Service theatre system for the trauma theatre at the Royal Gwent Hospital. Results demonstrated significant improvement in patient arrival time in the theatre suite; PDSA1 by 33 min (p≤0.001) and PDSA2 by 29 min (p≤0.001) and an earlier start of the first procedure; PDSA1 by 19 min (p=0.018) and PDSA2 by 26 min (p≤0.001). There was also increased mean operating time per list (PDSA1 +16 min and PDSA2 +33 min), increased total case number (PDSA1 +20 cases and PDSA2 +36 cases) and reduced cancellations (PDSA1 -2 cases and PDSA -5 cases) compared with our baseline data. We demonstrated that the introduction of a 'golden patient' to the trauma theatre list improved the start time and overall operating capacity for the trauma list. Continuing this project, we plan to introduce assessment of all patients with fractured neck of femur in a similar way to the 'golden patient' to continue improving trauma theatre efficiency and reduce case cancellations.

Bilateral Erector Spinae Plane Block for Surgery on the Posterior Aspect of the Neck: A Case Report.

The erector spinae plane block is an interfascial plane block whereby local anesthetic is injected within the plane deep to the erector spinae muscle and superficial to the transverse process. To date, it has been used to provide analgesia in thoracic, abdominal, and lumbar regions. We present the first reported case of bilateral erector spinae plane block being used to provide surgical anesthesia in the cervical region.

In vitro assessment of plutonium uptake and release using the human macrophage-like THP-1 cells.

Plutonium (Pu) intake by inhalation is one of the major potential consequences following an accident in the nuclear industry or after improvised nuclear device explosion. Macrophages are essential players in retention and clearance of inhaled compounds. However, the extent to which these phagocytic cells are involved in these processes highly depends on the solubility properties of the Pu deposited in the lungs. Our objectives were to develop an in vitro model representative of the human pulmonary macrophage capacity to internalize and release Pu compounds in presence or not of the chelating drug diethylenetriaminepentaacetate (DTPA). The monocyte cell line THP-1 was used after differentiation into macrophage-like cells. We assessed the cellular uptake of various forms of Pu which differ in their solubility, as well as the release of the internalized Pu. Results obtained with differentiated THP-1 cells are in good agreement with data from rat alveolar macrophages and fit well with in vivo data. In both cell types, Pu uptake and release depend upon Pu solubility and in all cases DTPA increases Pu release. The proposed model may provide a good complement to in vivo animal experiments and could be used in a first assessment to predict the fraction of Pu that could be potentially trapped, as well as the fraction available to chelating drugs.

A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis.

Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [(3)H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [(3)H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.

Decorporation of Pu/Am Actinides by Chelation Therapy: New Arguments in Favor of an Intracellular Component of DTPA Action.

Diethylenetriaminepentaacetic acid (DTPA) is currently still the only known chelating drug that can be used for decorporation of internalized plutonium (Pu) and americium (Am). It is generally assumed that chelation occurs only in biological fluids, thus preventing Pu/Am deposition in target tissues. We postulate that actinide chelation may also occur inside cells by a mechanism called "intracellular chelation". To test this hypothesis, rats were given DTPA either prior to (termed "prophylactic" treatment) or belatedly after (termed "delayed" treatment) Pu/Am injection. DTPA decorporation efficacy was systematically tested for both plutonium and americium. Both prophylactic and delayed DTPA elicited marked decreases in liver Pu/Am. These results can be explained by chelation within subcellular compartments where DTPA efficacy increased as a function of a favorable intracellular DTPA-to-actinide molar ratio. The efficacy of intracellular chelation of liver actinides decreased with the delay of treatment. This is probably explained by progressive actinide binding to the high-affinity ligand ferritin followed by migration to lysosomes. Intracellular chelation was reduced as the gap between prophylactic treatment and contamination increased. This may be explained by the reduction of the intracellular DTPA pool, which declined exponentially with time. Skeletal Pu/Am was also reduced by prophylactic and delayed DTPA treatments. This decorporation of bone actinides may mainly result from extracellular chelation on bone surfaces. This work provides converging evidence for the involvement of an intracellular component of DTPA action in the decorporation process. These results may help to improve the interpretation of biological data from DTPA-treated contamination cases and could be useful to model DTPA therapy regimens.