Academic literature on the topic 'Room-temperature susceptometry'

Abstract Introduction. Tissue iron measurements with magnetic resonance imaging (MRI) have given doctors a reliable way to monitor iron overload in thalassemias, sickle-cell disease and other disorders. However, MRI remains too expensive for widespread use in the countries where the largest numbers of patients with these disorders live. This abstract describes a test in human subjects of a potentially less expensive method of quantifying excess iron: measurement of liver iron concentrations (LIC) by magnetic susceptometry, using magnetic sensors that work at room temperature. Methods. The room-temperature susceptometer (RTS) in this study was a close copy of the one described by Maliken et al. [Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin. Ann. Hepatol. 2012;11:77-84]. LIC measurements with the RTS were compared to those of an existing SQUID (superconducting quantum interference device) biosusceptometer [Starr, TN et. al. A new generation SQUID biosusceptometer. Proceedings, 12th International Conference on Biomagnetism. 2000]. 84 patients, mostly with transfusion-dependent thalassemia major, participated in this comparison. Their LICs based on SQUID ranged from zero to 5250 μg/g wet weight, with median 920 μg/g and standard deviation 960 μg/g. Body-mass indices ranged from 16.6 to 31.7 kg/m2 (median 21.8 kg/m2, standard deviation 3.1 kg/m2). Liver-skin distances measured by ultrasound imaging ranged from 13.0 to 30.0 mm (median 17.5 mm, standard deviation 3.1 mm). For each patient, SQUID and RTS measurements were done in a single session. The agreement of the two susceptometers was assessed in terms of their Pearson product moment correlation coefficient r and the standard deviation σ of the differences between the SQUID results and the least-squares Deming regression line. This standard deviation was slightly dependent on the value of λ, the ratio of the variances of errors for the two susceptometers, that was assumed in the Deming regression. This dependence was estimated by calculating σ for a range of λ values. Results. LICs from RTS and SQUID had a Pearson product moment correlation coefficient r = 0.93. The differences between the two systems had a standard deviation σ = 363 μg/g assuming that the RTS's variance was four times the SQUID's and 353 μg/g assuming equal variances. As a point of reference, applying a similar analysis to published data yielded r = 0.975 and σ = 320 μg/g for a comparison of the Torino-based SQUID used in this study with another SQUID susceptometer at Hamburg [Engelhardt R et al. Agreement of liver iron quantification measurements with low Tc-SQUID biosusceptometers in Oakland, Torino and Hamburg. Elsevier International Congress Series 2007;1300: 279-282]. Conclusions. These results indicate that a less expensive susceptometer using room-temperature magnetic sensors can make liver iron measurements that are well correlated with those of the biopsy-validated SQUID technology. Based on the standard deviation of the differences between the two systems, the RTS used in this study was approaching accuracy levels that would be useful clinically, especially in screening patients for dangerously high iron. Since the RTS's errors in measurements on phantoms are significantly lower than those found in this study on human subjects, the room-temperature susceptometer's accuracy appears to be limited not by the noise of the room-temperature magnetic sensors, but by the relationship of the susceptometer to the patient's body. With improvement in areas such as patient positioning, measurement of the sensor-skin distance, and correction for the magnetic response of tissue between the liver and the susceptometer, low-cost susceptometers may ultimately achieve accuracies comparable to those of existing SQUIDs. Such technologies can potentially improve the management of iron overload, especially in regions where MRI is too expensive for routine use. Figure. Figure. Disclosures Piga: Acceleron: Research Funding; La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Apopharma: Honoraria, Research Funding; Bluebird Bio: Honoraria; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding. Avrin:Insight Magnetics: Employment, Other: Proprietor of company developing the study device, Patents & Royalties: Own rights to patents on the study device.

Abstract Introduction: Iron overload is frequently observed in diverse states ranging from thalassemia, sickle cell disease, hereditary hemochromatosis, transfusion-dependent anemias, cancer chemotherapy and chronic liver disease. Management of iron overload depends on the ability to quantify and monitor the patient's iron stores with precision. Organ iron measurement by relaxometry-based MRI techniques has become the current standard. MRI is expensive and has the added limitations of multiple existing methods and reduced dynamic range with 3 Tesla scanners. Liver iron measurements by magnetic susceptometers using superconductive quantum interference device (SQUID) technology are expensive and have limited availability. In this study an improved low-cost device, the room-temperature susceptometer (RTS, Insight Magnetics, San Diego, CA), was tested against the Model 5700 Ferritometer ® 3-Channel SQUID BioSusceptometer System (Tristan Technologies, Inc. San Diego, CA). Both systems quantify liver iron concentration (LIC) using bulk magnetic susceptibility. Where the SQUID uses an ultra-stable sensing system immersed in liquid helium, the RTS cancels the temperature and magnetic-field fluctuations inherent in an apparatus that works at room temperature. The RTS uses three main techniques to sense the very weak magnetic field produced by liver iron: (a) oscillatory magnetic fields that can be detected with high sensitivity using coils of ordinary copper wire, (b) field-producing and field-sensing coils to cancel the signal due to the applied magnetic field, and (c) movement of the sensing unit periodically toward and away from the patient so as to distinguish the patient's magnetic field response from the interfering signal caused by temperature fluctuations in the sensing system. Methods: This study compared measurements of LIC from RTS to those by the SQUID. The RTS in this study was modified from an earlier model to make the baseline reading more stable, and to increase the accuracy of the water reference measurement to which the patient's magnetic response is compared. The magnetic-field source and sensing coils were enlarged to increase the signal of the liver compared with that of the overlying tissue. LIC was measured once on the SQUID and once on the RTS at a single visit. Using ultrasound imaging, optimum liver measurement position was determined and marked with an x-y-positioning and z-distance sensing Locator Loop (Positronic Systemtechnik GmbH, Germany). The locator loop remained attached to the patient for measurements with both devices to preserve measurement location. LIC calculation was corrected for the susceptibility and geometry of the overlying tissue. Measurement results from SQUID and RTS were analyzed independently by two investigators. Results: Thirteen adults (10 with transfusion-dependent thalassemia and 3 controls) with body mass index (BMI) <25 were enrolled. All measurements were completed at a single visit with no failures. LIC values (µg/g wet-liver weight), ranged from -33 to 6493 with SQUID, and -305 to 7237 with RTS. In the three controls, the LIC was -33, 144 and 427 µg/g with SQUID, and -305, 451 and 230 µg/g with RTS. The overall correlation between the two methods was excellent, yielding an r2 = 0.976 and slope = 1.037 ± 0.068 (p<0.001, Fig 1). Bland-Altman analysis of percent-difference versus the average of the two methods showed bias -2.72 (95% limits of agreement -149.1 to 143.6) for all subjects, which improved to 1.94 (95% limits of agreement -41.1 to 45.3) when the average values below 350 µg/g (n=4) were excluded (Fig 2). The percent difference between the two methods was influenced by the subject's BMI (p=0.050 for all subjects; p=0.031 after excluding average LIC <350 µg/g), with the least difference observed in the BMI range of 20-23 Kg/m2. Conclusion: This study shows that, with the recent improvements in the RTS technology, LIC measurements now closely align with those using SQUID. The remaining difference between the two methods likely results from the models used to compensate for the overlying tissue. Further comparison of RTS to SQUID and MRI-based methods in diverse iron overload states is warranted in a larger study. This work may ultimately make low-cost noninvasive measurement of iron overload accessible to the large number of patients in the US, and to resource-limited countries around the world. Disclosures Lal: Bluebird Bio: Research Funding; Insight Magnetics: Research Funding; Terumo Corporation: Research Funding; Novartis: Research Funding; Celgene Corporation: Research Funding; La Jolla Pharmaceutical Company: Consultancy, Research Funding. Avrin:Insight Magnetics: Employment, Other: Proprietor of company developing the study device, Patents & Royalties: Own rights to patents on the study device. Weyhmiller:Insight Magnetics: Research Funding.

Abstract Accurate assessment of body-iron accumulation is essential for managing therapy of iron-chelating diseases characterized by iron overload such as thalassemia, hereditary hemochromatosis, myelodysplasia and other forms of severe anemia. At present, the gold standard to determine liver-iron concentration (LIC) is liver needle biopsy. In this work, we present an alternative non-invasive technique to measure LIC based on a room-temperature susceptometer. SQUID biosusceptometers and MRI are currently the only validated non-invasive methods for LIC measurements. However, SQUIDs are liquid helium-cooled superconducting devices, therefore costly and resource intensive. Furthermore, SQUIDs are only sensitive to a fraction of the liver volume because of their magnetic configuration. MRI requires large magnets with dedicated software and hardware, trained operators, and is accurate only at low iron concentration. The susceptometer presented herein measures iron overload in the whole liver, as the entire human torso fits within its region of sensitivity. Since all of its components operate at room temperature, this susceptometer is more affordable then competing techniques and can reach a wider hospital base. The study was approved by the local Ethics Committee and all subjects gave informed consent. Since February 2005, 40 patients (30 thalassemia major or intermedia, 5 hereditary hemochromatosis, 5 other severe anemia) and 68 healthy volunteers have been measured. The signal picked up by the susceptometer has two sources: an overall magnetic background of the torso and an eventual contribution from liver iron excess. After measuring the magnetic signature of a patient, statistical analysis methods and neural-network simulations (trained using the control data) are employed to estimate the background signal, given the patient anthropometric data. Liver-iron overload is then determined by subtraction of the estimated background from the total measured signal. The refinement of the methodology is in progress and, at present, the error in liver iron is about 1g (SD), corresponding to typical concentrations of 0.5 mg/cm^3. A correlation study between iron overload and blood serum-ferritin concentration in the patient population attained a correlation coefficient R~0.73. Comparison with measurements of LIC via SQUID susceptometry on a subset of 30 patients participating in the present study (carried out by Dr. A. Piga at Ospedale S. Anna, Torino, Italy) yields a correlation coefficient R~0.77. Four patients (3 thalassemia major, 1 hereditary hemochromatosis) under intensive iron depletive therapy have been measured at least twice; our estimate of liver iron reduction is compatible with the clinical data (R~0.76). Comparison with LIC measured via biopsy is in progress. All comparison were blinded. These preliminary results indicate that possible applications of this non-invasive, full-body susceptometer include monitoring the efficacy of the therapy as well as improving the diagnosis and care management of patients with iron overload. Figure Figure

Il lavoro di dottorato ha coinvolto tre principali aree di ricerca biomedica. Nella prima area, abbiamo mirato a valutare se le misure del tempo di rilassamento T1 in Risonanza Magnetica possono contribuire ad individuare dei predittori strutturali di lievi disturbi cognitivi in pazienti con forma Recidivante-Remittente di Sclerosi Multipla(RRMS). Ventinove controlli sani (HC) e quarantanove RRMS pazienti sono stati sottoposti a Risonanza magnetica a 3T per acquisire in maniera ottimale per la zona corticale e per la sostanza bianca (WML), i tempi di rilassamento T1 (rt), la conta delle lesioni e il volume. Nella WML e in quelle di tipo CL I (sostanza bianca - grigia mista), i T1 rt z-score sono risultati, significativamente, più lunghi rispetto ai tessuti dei controlli HC (p<0.001 e p<0.01, rispettivamente), indice di un’impoverimento del tessuto cerebrale. L'analisi di regressione multivariata ha rivelato che: i T1 rt z-score nelle lesioni corticali sono predittori indipendenti del recupero della memoria a lungo termine (p=0.01), i T1 z -score nella lesioni corticali della materia bianca sono predittori indipendenti del deficit relativi all’attenzione prolungata e all’elaborazione delle informazioni (p=0,02) ; Nella seconda, descriviamo un suscettometro biomagnetico a temperatura ambiente in grado di quantificare il sovraccarico di ferro nel fegato. Tramite un campo magnetico modulato elettronicamente, il sistema riesce a misurare segnali magnetici 108 volte più piccoli del campo applicato. Il rumore meccanico del suscettometro a temperatura ambiente viene minimizzato e il drift termico viene monitorato da un sistema automatico di bilanciamento. Abbiamo testato e calibrato lo strumento utilizzando un fantoccio riempito con una soluzione di esacloruro esaidrato II di ferro, ottenendo come correlazione R = 0,98 tra la massima risposta del suscettometro e la concentrazione di ferro. Queste misure indicano che per garantire una buon funzionamento dello strumento con una variabilità del segnale di uscita pari al 4-5%, eguale a circa 500ugr/gr di ferro, il tempo di acquisizione deve essere minore o uguale a 8 secondi. Nela terza area, un'analisi agli elementi finiti del modello 3D anatomicamente dettagliato del piede umano è il risultato finale della segmentazione 3D, secondo tecniche di ricostruzione applicate ad immagini standard DICOM di scansione a Tomografia Computerizzata, in congiunzione con la modellazione 3D assistita e dell’analisi agli elementi finiti (FEA). In questo modello la reale morfologia del cuscinetto adiposo plantare è stato considerata: è stato dimostrato giocare un ruolo molto importante durante il contatto con il terreno. Per ottenere i dati sperimentali da confrontare con le predizioni del modello 3D del piede, un esame posturografico statico su una pedana baropodometrica è stato effettuato. La pressione sperimentale del contatto plantare è risultata, qualitativamente, comparabile con i risultati predetti dall’analisi agli elementi finiti, principalmente, confrontando i valori sperimentali con i valori massimi delle pressioni in corrispondenza delle zona centrali del tallone e sotto le teste metatarsali.
The PhD work involved three main biomedical research areas. In the first, we aimed at assessing whether T1 relaxometry measurements may help identifying structural predictors of mild cognitive impairments in patients with relapsing-remitting multiple sclerosis. Twenty-nine healthy controls and forty-nine RRMS patients underwent at high resolution 3T magnetic resonance imaging to obtain optimal cortical and white matter lesion count/volume as well as T1 relaxation times (rt). In WML and CL type I (mixed white-gray matter), T1 rt z-scores were significantly longer than in HC tissue (p<0.001 and p<0.01 respectively), indicating loss of structure. Multivariate analysis revealed T1 rt z-scores in CL type I were independent predictors of long term retrieval (p=0.01), T1 z-score relaxation time in white matter cortical lesions were independent predictors of sustained attention and information processing (p=0.02); In the second, we describe a biomagnetic susceptometer at room-temperature to quantify liver iron overload. By electronically modulated magnetic field, the magnetic system measure magnetic signal 108 times weaker than field applied. The mechanical noise of room-temperature susceptometer is cancelled and thermal drift is monitored by an automatic balance control system. We have tested and calibrated the system using cylindrical phantom filled with hexahydrated iron II choloride solution, obtaining the correlation (R=0.98) of the maximum variation in the responses of the susceptometer. These measures indicate that the acquisition time must be less than 8 seconds to guarantee an output signal variability to about 4-5%, equal to 500ugr/grwet of iron. In the third, a 3D anatomically detailed finite element analysis human foot model is final results of density segmentation 3D reconstruction techiniques applied in Computed Tomography(CT) scan DICOM standard images in conjunctions with 3D finite element analysis(FEA) modeling. In this model the real morphology of plantar fat pad has been considered: it was shown to play a very important role during the contact with the ground. To obtain the experimental data to compare the predictions of 3D foot model, a posturography static examination test on a baropodometric platform has been carried. The experimental plantar contact pressure is, qualitatively, comparable with FEA predicted results, nominally, the peak pressure value zones at the centre heel region and beneath the metatarsal heads.