Evaluation of a semi-automated approach for FDG PET image analysis for routine clinical application in patients with multiple myeloma.

Background: FDG PET/CT is a tool for assessing response to therapy in various cancers, and may provide an earlier biomarker of clinical response. We developed a novel semi-automated approach for analyzing FDG PET/CT images in patients with multiple myeloma (MM) to standardize FDG PET application.

Methods: Patients (n = 8) with relapsed/refractory MM from the Phase 2 study (NCT02899052) of venetoclax plus carfilzomib and dexamethasone underwent FDG PET/CT at baseline and up to two timepoints during treatment.

Intrathecal Tc-DTPA imaging of molecular passage from lumbar cerebrospinal fluid to brain and periphery in humans.

Introduction: Cerebrospinal fluid (CSF) molecular exchange with brain interstitial fluid (ISF) and periphery is implicated in neurological disorders but needs better quantitative clinical assessment approaches.

Methods: Following intrathecal (ITH) dosing via lumbar puncture, Technetium-99 m (Tc-) diethylenetriaminepentaacetic acid (DTPA) imaging was used to quantify neuraxial spread, CSF-brain molecular exchange, and CSF-peripheral clearance in 15 normal human volunteers. The effect of experimental convection manipulation on these processes was also assessed.

Dual-Isotope Cryoimaging Quantitative Autoradiography: Investigating Antibody-Drug Conjugate Distribution and Payload Delivery Through Imaging.

In vitro properties of antibody-drug conjugates (ADCs) such as binding, internalization, and cytotoxicity are often well characterized before in vivo studies. Interpretation of in vivo studies might be significantly enhanced by molecular imaging tools. We present here a dual-isotope cryoimaging quantitative autoradiography (CIQA) methodology combined with advanced 3-dimensional imaging and analysis allowing for the simultaneous study of both antibody and payload distribution in tissues of interest in a preclinical setting.

Three-Dimensional Dosimetry for Radiation Safety Estimates from Intrathecal Administration.

Intrathecal administration is of growing interest for drug delivery, and its utility is being increasingly investigated through imaging. In this work, the 3-dimensional Voxel-Based Internal Dosimetry Application (VIDA) and 4D Extended Cardiac Torso Phantom (XCAT) were extended to provide radiation safety estimates specific to intrathecal administration. The 3-dimensional VIDA dosimetry application Monte Carlo simulation was run using a modified XCAT phantom with additional and edited cerebrospinal fluid (CSF) regions to produce voxel-level absorbed dose per unit cumulated activity maps for 9 selected source regions.

Automated segmentation of MR imaging to determine normative central nervous system cerebrospinal fluid volumes in healthy volunteers.

An accurate non-invasive method to determine total body cerebrospinal fluid volume has a number of potential diagnostic and therapeutic applications. Herein we describe a technique for automated segmentation of total body MRI data to determine cranial and spinal CSF volume in 15 healthy adults. These in vivo estimates of CSF volume exceed the standard reported volume of 150mL in human adults and provide normative data for diagnosis of disease states such as hydrocephalus and therapy including pharmacologic dosimetry.

Dynamic dual-isotope molecular imaging elucidates principles for optimizing intrathecal drug delivery.

The intrathecal (IT) dosing route offers a seemingly obvious solution for delivering drugs directly to the central nervous system. However, gaps in understanding drug molecule behavior within the anatomically and kinetically unique environment of the mammalian IT space have impeded the establishment of pharmacokinetic principles for optimizing regional drug exposure along the neuraxis. Here, we have utilized high-resolution single-photon emission tomography with X-ray computed tomography to study the behavior of multiple molecular imaging tracers following an IT bolus injection, with supporting histology, autoradiography, block-face tomography, and MRI.

Regional, kinetic [(18)F]FDG PET imaging of a unilateral Parkinsonian animal model.

Positron emission tomography (PET) imaging with the glucose analog 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F] FDG) has demonstrated clinical utility for the monitoring of brain glucose metabolism alteration in progressive neurodegenerative diseases. We examined dynamic [(18)F]FDG PET imaging and kinetic modeling of atlas-based regions to evaluate regional changes in the cerebral metabolic rate of glucose in the widely-used 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. Following a bolus injection of 18.

Regional particle size dependent deposition of inhaled aerosols in rats and mice.

Context: The current data analysis tools in nuclear medicine have not been used to evaluate intra organ regional deposition patterns of pharmaceutical aerosols in preclinical species.

Objective: This study evaluates aerosol deposition patterns as a function of particle size in rats and mice using novel image analysis techniques.

Materials And Method: Mice and rats were exposed to radiolabeled polydisperse aerosols at 0.

Assessing antibody pharmacokinetics in mice with in vivo imaging.

Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements of antibody distribution in mouse models. This article reviews the strengths and limitations of in vivo antibody imaging methods with a focus on positron emission tomography and single-photon emission computed tomography and a brief discussion of the role of optical imaging in this application. A description of the basic principles behind the imaging techniques is provided along with a discussion of radiolabeling methods relevant to antibodies.

Maximum-Likelihood Estimation With a Contracting-Grid Search Algorithm.

A fast search algorithm capable of operating in multi-dimensional spaces is introduced. As a sample application, we demonstrate its utility in the 2D and 3D maximum-likelihood position-estimation problem that arises in the processing of PMT signals to derive interaction locations in compact gamma cameras. We demonstrate that the algorithm can be parallelized in pipelines, and thereby efficiently implemented in specialized hardware, such as field-programmable gate arrays (FPGAs).

Adaptive SPECT.

Adaptive imaging systems alter their data-acquisition configuration or protocol in response to the image information received. An adaptive pinhole single-photon emission computed tomography (SPECT) system might acquire an initial scout image to obtain preliminary information about the radiotracer distribution and then adjust the configuration or sizes of the pinholes, the magnifications, or the projection angles in order to improve performance. This paper briefly describes two small-animal SPECT systems that allow this flexibility and then presents a framework for evaluating adaptive systems in general, and adaptive SPECT systems in particular.

Hardware assessment using the multi-module, multi-resolution system (M3R): a signal-detection study.

The multi-module, multi-resolution system (M3R) is used for hardware assessment in objective, task-based signal detection studies in projection data. A phantom capable of generating multiple realizations of a random textured background is introduced. Measured backgrounds from this phantom are used along with simulated lumpy and uniform backgrounds to investigate signal-to-noise ratio as a function of exposure time.

The multi-module, multi-resolution system (M3R): a novel small-animal SPECT system.

We have designed and built an inexpensive, high-resolution, tomographic imaging system, dubbed the multi-module, multi-resolution system, or M3R. Slots machined into the system shielding allow for the interchange of pinhole plates, enabling the system to operate over a wide range of magnifications and with virtually any desired pinhole configuration. The flexibility of the system allows system optimization for specific imaging tasks and also allows for modifications necessary due to improved detectors, electronics, and knowledge of system construction (e.

Evaluation of hardware in a small-animal SPECT system using reconstructed images.

Evaluation of imaging hardware represents a vital component of system design. In small-animal SPECT imaging, this evaluation has become increasingly difficult with the emergence of multi-pinhole apertures and adaptive, or patient-specific, imaging. This paper will describe two methods for hardware evaluation using reconstructed images.

Experimental task-based optimization of a four-camera variable-pinhole small-animal SPECT system.

We have previously utilized lumpy object models and simulated imaging systems in conjunction with the ideal observer to compute figures of merit for hardware optimization. In this paper, we describe the development of methods and phantoms necessary to validate or experimentally carry out these optimizations. Our study was conducted on a four-camera small-animal SPECT system that employs interchangeable pinhole plates to operate under a variety of pinhole configurations and magnifications (representing optimizable system parameters).