GATE Validation of Standard Dual Energy Corrections in Small Animal SPECT-CT

<div><p>This paper addresses ¹²³I and ¹²⁵I dual isotope SPECT imaging, which can be challenging because of spectrum overlap in the low energy spectrums of these isotopes. We first quantify the contribution of low-energy photons from each isotope using GATE-based Monte Carlo simulations for the MOBY mouse phantom. We then describe and analyze a simple, but effective method that uses the ratio of detected low and high energy ¹²³I activity to separate the mixed low energy ¹²³I and ¹²⁵I activities. Performance is compared with correction methods used in conventional tissue biodistribution techniques. The results indicate that the spectrum overlap effects can be significantly reduced, if not entirely eliminated, when attenuation and scatter is either absent or corrected for using standard methods. In particular, we show that relative activity levels of the two isotopes can be accurately estimated for a wide range of organs and provide quantitative validation that standard methods for spectrum overlap correction provide reasonable estimates for reasonable corrections in small-animal SPECT/CT imaging.</p></div

Illustrations of model components.

<p>a). GATE model of Siemens Inveon SPECT system configured with two MGP collimators. b). MWB collimator. c). MOBY attenuation phantom.</p

Energy spectra of ¹²³I and ¹²⁵I for the MGP collimator.

<p>Energy spectra of ¹²³I and ¹²⁵I for the MGP collimator.</p

Comparison of real and simulated data.

<p>The top row shows real data for the uncorrected low energy window, high energy window, and the corrected low energy window. The bottom row shows the same information but for the simulated MOBY phantom data.</p

Estimated low-to-high energy (e123) ratios for selected organs in different sized mice.

<p>Estimated low-to-high energy (e123) ratios for selected organs in different sized mice.</p

Stacked bar plots of energy ratios and relative activity measurements.

<p>a). Low-to-high energy ratio e123 under different imaging conditions. b). Total ¹²³I activity in both high and low-energy windows.</p

Relative estimation error for three different imaging conditions: Ideal (no scatter medium), scatter and attenuation medium without corrections, and scatter and attenuation medium with corrections.

<p>Relative estimation error for three different imaging conditions: Ideal (no scatter medium), scatter and attenuation medium without corrections, and scatter and attenuation medium with corrections.</p

Immunoglobulin Light Chains Form an Extensive and Highly Ordered Fibril Involving the N- and C-Termini

Light-chain (AL)-associated amyloidosis is a systemic disorder involving the formation and deposition of immunoglobulin AL fibrils in various bodily organs. One severe instance of AL disease is exhibited by the patient-derived variable domain (V_L) of the light chain AL-09, a 108 amino acid residue protein containing seven mutations relative to the corresponding germline protein, κI O18/O8 V_L. Previous work has demonstrated that the thermodynamic stability of native AL-09 V_L is greatly lowered by two of these mutations, Y87H and N34I, whereas a third mutation, K42Q, further increases the kinetics of fibril formation. However, detailed knowledge regarding the residues that are responsible for stabilizing the misfolded fibril structure is lacking. In this study, using solid-state NMR spectroscopy, we show that the majority of the AL-09 V_L sequence is immobilized in the fibrils and that the N- and C-terminal portions of the sequence are particularly well-structured. Thus, AL-09 V_L forms an extensively ordered and β-strand-rich fibril structure. Furthermore, we demonstrate that the predominant β-sheet secondary structure and rigidity observed for in vitro prepared AL-09 V_L fibrils are qualitatively similar to those observed for AL fibrils extracted from postmortem human spleen tissue, suggesting that this conformation may be representative of a common feature of AL fibrils

Growth of NP diameter as a function of shell addition as measured by TEM.

<p>Growth of NP diameter as a function of shell addition as measured by TEM.</p

MAb 201b antibody conjugation to multi-layered NPs.

<p>MAb 201b antibody conjugation to multi-layered NPs.</p