Unveiling the Temporal Aspect of MRI Tattoo Reactions: A Prospective Evaluation of a Newly-Acquired Tattoo with Multiple MRI Scans.

BACKGROUND Over the past 30 years, painful reactions during magnetic resonance imaging (MRI) in tattooed individuals have been sporadically reported. These complications manifest as burning pain in tattooed skin areas, occasionally with swelling and redness, often leading to termination of the scanning. The exact cause is unclear, but iron oxide pigments in permanent make-up or elements in carbon black tattoos may play a role. Additionally, factors like tattoo age, design, and color may influence reactions. The existing literature lacks comprehensive evidence, leaving many questions unanswered. CASE REPORT We present the unique case of a young man who experienced recurring painful reactions in a recently applied black tattoo during multiple MRI scans. Despite the absence of ferrimagnetic ingredients in the tattoo ink, the patient reported intense burning sensations along with transient erythema and edema. Interestingly, the severity of these reactions gradually decreased over time, suggesting a time-dependent factor contributing to the problem. This finding highlights the potential influence of pigment particle density in the skin on the severity and risk of MRI interactions. We hypothesize that the painful sensations could be triggered by excitation of dermal C-fibers by conductive elements in the tattoo ink, likely carbon particles. CONCLUSIONS Our case study highlights that MRI-induced tattoo reactions may gradually decrease over time. While MRI scans occasionally can cause transient reactions in tattoos, they do not result in permanent skin damage and remain a safe and essential diagnostic tool. Further research is needed to understand the mechanisms behind these reactions and explore preventive measures.

MRI-Induced Neurosensory Events in Decorative Black Tattoos: Study by Advanced Experimental Methods.

Adverse reactions in tattooed skin during magnetic resonance imaging (MRI) are rare but well known. Previous reports describe sudden burning pain in tattooed skin, sometimes accompanied by mild erythema and oedema when entering MRI scanners. The pathophysiology remains unclear, but simple direct thermal heating can be excluded. It has been hypothesized that MRI-triggered torque and traction create neural sensations from magnetic pigment particles. However, this case enlightens yet another possible mechanism. We present a 35-year-old woman experiencing reoccurring stinging sensations in three decorative black tattoos just seconds after the initiation of the MRI. Single-blind tests with handheld power magnets or a dummy could reproduce painful subjective feelings in her tattooed skin. Similar events were provoked during re-evaluation with MRI. Surprisingly, chemical analyses and electron microscopy of skin samples revealed carbon black as the colouring agent - no iron-based solids were detected. Our case demonstrates that MRI tattoo reactions are not limited to magnetic contaminants alone. More distinct subgroups of MRI-induced reactions may occur. We hypothesize that radiofrequency induction of surface currents in black carbon particles adjacent to sensory axons in the dermis may lead to neurosensations.

Geometric distortions in clinical MRI sequences for radiotherapy: insights gained from a multicenter investigation.

BACKGROUND: As magnetic resonance imaging (MRI) becomes increasingly integrated into radiotherapy (RT) for enhanced treatment planning and adaptation, the inherent geometric distortion in acquired MR images pose a potential challenge to treatment accuracy. This study aimed to evaluate the geometric distortion levels in the clinical MRI protocols used across Danish RT centers and discuss influence of specific sequence parameters. Based on the variety in geometric performance across centers, we assess if harmonization of MRI sequences is a relevant measure. MATERIALS AND METHODS: Nine centers participated with 12 MRI scanners and MRI-Linacs (MRL). Using a travelling phantom approach, a reference MRI sequence was used to assess variation in baseline distortion level between scanners. The phantom was also scanned with local clinical MRI sequences for brain, head/neck (H/N), abdomen, and pelvis. The influence of echo time, receiver bandwidth, image weighting, and 2D/3D acquisition was investigated. RESULTS: We found a large variation in geometric accuracy across 93 clinical sequences examined, exceeding the baseline variation found between MRI scanners (σ = 0.22 mm), except for abdominal sequences where the variation was lower. Brain and abdominal sequences showed lowest distortion levels ([0.22, 2.26] mm), and a large variation in performance was found for H/N and pelvic sequences ([0.19, 4.07] mm). Post hoc analyses revealed that distortion levels decreased with increasing bandwidth and a less clear increase in distortion levels with increasing echo time. 3D MRI sequences had lower distortion levels than 2D (median of 1.10 and 2.10 mm, respectively), and in DWI sequences, the echo-planar imaging read-out resulted in highest distortion levels. CONCLUSION: There is a large variation in the geometric distortion levels of clinical MRI sequences across Danish RT centers, and between anatomical sites. The large variation observed makes harmonization of MRI sequences across institutions and adoption of practices from well-performing anatomical sites, a relevant measure within RT.

On the mechanism of painful burn sensation in tattoos on magnetic resonance imaging (MRI). Magnetic substances in tattoo inks used for permanent makeup (PMU) identified: Magnetite, goethite, and hematite.

BACKGROUND: Persons with cosmetic tattoos occasionally experience severe pain and burning sensation on magnetic resonance imaging (MRI). OBJECTIVE: To explore the culprit magnetic substances in commonly used permanent makeup inks. MATERIAL AND METHODS: 20 inks used for cosmetic tattooing of eyebrows, eyeliners, and lips were selected. Ink bottles were tested for magnetic behavior with a neodymium magnet. Eight iron oxide inks qualified for the final study. Metals were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The magnetic fraction of inks was isolated and analyzed by X-ray fluorescence (XRF). Magnetic iron compounds were characterized by Mössbauer spectroscopy and powder X-ray diffraction (XRD). RESULTS: ICP-MS showed iron in all magnetic samples, and some nickel and chromium. Mössbauer spectroscopy and XRD detected ferromagnetic minerals, particularly magnetite, followed by goethite and hematite. CONCLUSION: This original study of cosmetic ink stock products made with iron oxide pigments reports magnetic impurities in inks for cosmetic tattooing, e.g., magnetite, goethite, and hematite. These may be the main cause of MRI burn sensation in cosmetic tattoos. The mechanism behind sensations is hypothesized to be induction of electrical stimuli of axons from periaxonal pigment/impurity activated by magnetic force. Magnetite is considered the lead culprit.

Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry.

BACKGROUND AND PURPOSE: With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd3+(aq), can be released in patients if the organic ligand is degraded by the radiation. In this study, T1 relaxation measurements were performed to study the effect of radiation on three GBCAs. MATERIALS AND METHODS: GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100 mM. Measurements were performed on a 500 MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100 Gy. The lower detection limit of Gd3+(aq) was established by estimating the overall measurement uncertainty and comparing to corresponding changes in R1 when replacing chelated Gd3+ with gadolinium nitrate at predefined percentages. RESULTS: The overall measurement uncertainty was estimated to ±0.0053 ms-1, corresponding to Gd3+(aq) detection levels 1%-1.5% or 1-4.5 micro molar at clinical GBCA dosage. No detectable differences in R1 were observed between irradiated and non-irradiated samples for any GBCA. CONCLUSIONS: This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.

Tattoo complications and magnetic resonance imaging: a comprehensive review of the literature.

Tattooed patients undergoing magnetic resonance imaging (MRI) can develop cutaneous complications during the procedure. Our aim was to review all published case reports on MRI-induced tattoo complications to identify a possible pattern. So far, 17 cases have been reported. Five (29%) of the cases were in cosmetic tattoos. Symptoms are abrupt and painful with fast onset during MRI, sometimes requiring termination of the procedure. Clinical signs are absent or manifested as inflammation sensed as burning. No thermal skin burns have been recognized. Full recovery is fast, with no sequelae. MRI-induced tattoo complications are uncommon. Patients with cosmetic and traditional tattoos can undergo routine MRI.

Electrochemotherapy for colorectal cancer using endoscopic electroporation: a phase 1 clinical study.

Background and study aims Electrochemotherapy is an anticancer treatment that uses electric pulses to facilitate uptake of chemotherapeutic drugs in tumor cells and has proven to have a high local cytotoxic effect with minimal adverse events. Electrochemotherapy has mostly been used in treatment of cutaneous metastases but development of a new endoscopic electrode device has made treatment of colorectal tumors possible. This first-in-man multicenter phase I study investigated safety and efficacy of electrochemotherapy using endoscopic electroporation in patients with colorectal tumors. Patients and methods Seven patients with colorectal tumors who were deemed ineligible for or had declined standard treatment were included. They were treated with bleomycin either intratumorally or intravenously and the electric pulses were delivered through the endoscopic electrode device. Safety and efficacy were assessed clinically and by scans immediately after treatment and adverse events were reported. Response was evaluated up to 6 months after treatment by scans (magnetic resonance imaging or computed tomography) and endoscopic examinations. Results Seven patients aged 62 to 88 years with multiple comorbidities were included and had one or two treatments each. Post-treatment scans showed tumor responses in the treated areas and no damage to surrounding tissues. Only a few grade one adverse events were reported. Three patients had preoperative rectal bleeding, of which two reported cessation of bleeding and one reported decreased bleeding. Conclusion This first-in-man study shows that electrochemotherapy for colorectal tumors using the endoscopic electrode device can induce local tumor response and is safe also for fragile elderly patients with comorbidities.

Diffusion MRI outlined viable tumour volume beats GTV in intra-treatment stratification of outcome.

BACKGROUND AND PURPOSE: In radiotherapy, treatment response is generally evaluated many weeks after end of the treatment course. If the treatment outcome could be predicted during radiotherapy better tumour control could be achieved through timely adaptation of the treatment strategy. In this study intra-treatment change based on the diffusion MRI outlined viable tumour volume (VTV) was assessed and compared to the standard GTV to study their outcome prediction capacity. MATERIALS AND METHODS: Thirty-eight brain metastases from twenty-one cancer patients were analysed in this prospective trial. Diffusion and structural MRI was acquired on a 1 T machine before, during, and at follow-up 2-3 months after radiotherapy. The VTV was defined as a region with high cellularity using high b-value diffusion MRI scans. Further, the diffusivity of the VTV was derived as the apparent diffusion coefficient (ADC). Treatment outcome was determined using RECIST defined bounds in the T1W MRI follow-up scan. Longitudinal statistical analysis was performed using a linear mixed effect model. RESULTS: The GTV declined in both responding and non-responding (significantly) tumours with inseparable rates during radiotherapy. The VTV volume fraction reduced significantly in the responding tumours only. The ADC of the VTV increased significantly in responding metastases whereas it decreased in non-responding metastases. Furthermore, no association between baseline tumour size or primary disease and outcome was observed. CONCLUSION: GTV size change during radiotherapy is not a reliable predictor of outcome in brain metastases. On the other hand, change in the volume fraction of VTV and diffusivity of VTV shows ability to stratify treatment outcome.

Home-based aerobic exercise in patients with lacunar stroke: Design of the HITPALS randomized controlled trial.

BACKGROUND: The effects of physical exercise in patients with lacunar stroke, seem promising in secondary prevention and only few studies have investigated the effect of high-intensity interval training in patients with lacunar stroke. This study will be investigating whether high-intensity interval training improves cardiovascular fitness as well as cognitive- and endothelial function and potentially attenuating the risk of recurrent stroke. METHODS: A randomized controlled trial evaluating 12 weeks of home-based, high-intensity interval training compared with usual care. The intervention group will be exercising 15 min a day, 5 days a week, for 12 weeks. Outcomes will be evaluated at baseline, three, six and twelve months post-stroke with 'The Graded Cycling Test with Talk Test' as the primary outcome registered as power output in Watts. Additionally, an annually register-based follow-up will be performed for 5 years from date of inclusion with a composite endpoint of cardiovascular disease or death. Secondary outcomes will be: physical activity, endothelial response, mental well-being, cognition, mood, fatigue, stress, and MRI scan. DISCUSSION: This study is going to show if early initiated home-based high-intensity interval training is feasible and effective in patients with lacunar stroke. A self-chosen aerobic exercise modality allows a realistic implementation of practice, together with greater chance of long-term adherence. A limitation of the study is that recruitment bias cannot be ruled out, as there may be a preferential enrolment of patients who are self-motivated to engage in exercise.

The DAHANCA 32 study: Electrochemotherapy for recurrent mucosal head and neck cancer.

BACKGROUND: Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer. METHODS: Phase II clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose-positron emission tomography scanning, safety, toxicity, pain score, and quality-of-life questionnaires. RESULTS: Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression. CONCLUSION: Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.

Gene therapy for patients with advanced solid tumors: a phase I study using gene electrotransfer to muscle with the integrin inhibitor plasmid AMEP.

BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by adverse events registration, visual analog scale (VAS) after procedure and magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid AMEP in plasma and urine was determined by quantitative polymerase chain reaction. Response was evaluated by positron emission tomography-computed tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at dose levels from 50 to 250 µg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could not be detected, which could be due to the limit of detection. No objective responses were seen. CONCLUSIONS: Gene electrotransfer of plasmid AMEP was found to be safe and tolerable. No objective responses were observed but other DNA drugs may be tested in the future using this procedure.

Biparametric versus multiparametric MRI in the diagnosis of prostate cancer.

BACKGROUND: Since multiparametric magnetic resonance imaging (mp-MRI) of the prostate exceeds 30 min, minimizing the evaluation time of significant (Gleason scores > 6) prostate cancer (PCa) would be beneficial. A reduced protocol might be sufficient for the diagnosis. PURPOSE: To study whether a short unenhanced biparametric MRI (bp-MRI) matches mp-MRI in detecting significant PCa. MATERIAL AND METHODS: A total of 204 men (median age, 65 years; mean ± SD, 64.1; range 45-75 years; median serum PSA level, 14 ng/mL; range, 2.2-120 ng/mL; median prostate volume, 60 mL; range, 23-263 mL) fulfilled the criteria for being enrolled. They underwent mp-MRI and prostate biopsy from January through June 2014. Of the included patients, 9.3% underwent prostatectomy, 90.7% had TRUS-bx, and 10.8 had MRI-targeted TRUS-bx. Two radiologists separately assessed the mp-MRI examination (T2-weighted [T2W] imaging, diffusion-weighted imaging [DWI], apparent diffusion coefficient map [ADC-map] and dynamic contrast-enhanced imaging [DCE]). Two months later, the bp-MRI version (T2W imaging, DWI, and ADC-map) was evaluated. RESULTS: Reader 1: Assessing mp-MRI: 0 false negatives, sensitivity of 1, and specificity 0.04. Assessing bp-MRI: four false negatives, sensitivity of 0.94, and specificity 0.15. Reader 2: Assessing mp-MRI: five false negatives, sensitivity of 0.93, and specificity 0.16. Assessing bp-MRI: three false negatives, sensitivity of 0.96, and specificity 0.15. Intra-reader agreement Cohen's Kappa (κ) was 0.87 for reader 1 (95% confidence interval [CI], 0.83-0.92) and 0.84 for reader 2 (95% CI 0.78-0.89). CONCLUSION: Bp-MRI is as good as mp-MRI at detecting PCa. A large prospective study seems to be strongly warranted.

Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution.

Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of ß-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.

Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice.

OBJECTIVE: Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-ß family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling through systemic fstl3 over-expression protects against diet-induced obesity and insulin resistance. METHODS: Fstl3 was over-expressed by DNA electrotransfer in tibialis anterior, quadriceps and gastrocnemius muscles in female C57BL/C mice, and the mice were subsequently randomized to chow or high-fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were determined. RESULTS: Fstl3 over-expression reduced fat accumulation during high-fat feeding by 16%, and liver fat by 50%, as determined by MRI. No changes in body weight were observed, while the weight of the transfected muscles increased by 10%. No transcriptional changes were found in the subcutaneous adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin/glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24h fasting. CONCLUSION: Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content.