TL;DR: In this article, various 3D additive manufacturing approaches are reviewed in terms of two important figures of merit: maximum voxel printing rate and minimum Voxel size, which significantly surpass previous best values.
Abstract: Herein, various 3D additive manufacturing approaches are reviewed in terms of two important figures of merit: maximum voxel printing rate and minimum voxel size. Voxel sizes from several 100 µm down to the 100 nm scale are covered. Original results on multifocus two-photon printing at around voxel printing rates of 107 voxels s−1 are presented in this context, which significantly surpass previous best values. These advances are illustrated by and applied to the making of microstructured 3D (chiral) mechanical metamaterials that are composed of more than one-hundred-thousand unit cells in three dimensions. Previous best values for unit cells of similar complexity are smaller by two orders of magnitude.
TL;DR: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.
Abstract: Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.
TL;DR: PET with 68Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.
Abstract: To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with 68Ga-labelled somatostatin analogue. In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4 GBq 177Lu-DOTATOC or 177Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3 months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1 h after administration in PRRT were compared to the maximum standardized uptake values (SUVmax) in the meningiomas from the PET scans before and after therapy. The median SUVmax in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11 cm³ was a median of 23.4 × 10−6 (range 0.4 × 10−6 to 68.3 × 10−6). A strong correlation was observed between SUVmax and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman’s rank test, P < 0.01). Excluding one patient who showed large differences in biokinetics between PET and PRRT and another patient with incomplete data, linear regression analysis indicated significant correlations between SUVmax and the therapeutic uptake (r = 0.95) and between SUVmax and the maximum voxel dose from PRRT (r = 0.76). Observed absolute deviations from the values expected from regression were a median of 5.6 × 10−6 (maximum 9.3 × 10−6) for the voxel fractional radionuclide uptake and 0.40 Gy per GBq (maximum 0.85 Gy per GBq) 177Lu for the voxel dose from PRRT. PET with 68Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.
TL;DR: In this article, the authors used two-photon lithography (TPL) on positive photoresist AZ 4562 for the fabrication of a microfluidic device in a single lithography and development step.
Abstract: Organ-on-chip (OoC) devices are increasingly used for biomedical research and to speed up the process of bringing a medicinal drug from the lab to the market. The technology also addresses ethical issues linked to animal testing as it offers a reduction in animal experiments through its possibility to mimic the environment in the human body. Hence, it produces more relevant results than plain cell-culture experiments, while still sharing the possibility of high-throughput testing by simultaneously operating many devices in parallel. The main components of an OoC device are microfluidic channels and porous membranes. Current chips are often assembled from several parts. In the development phase a small change in design will cause a delay in the research because a new prototype has to be built again step-by-step. This research addresses this problem by targeting the fabrication of a microfluidic device in a single lithography and development step. A device consisting of two crossed channels at different heights separated by a membrane was chosen. The manufacturing method used was two-photon lithography (TPL) on positive photoresist AZ 4562. TPL exploits the fact that two-photon absorption non-linearly depends on the light intensity. The required intensity is only achieved in a small volume around the focal point, called the voxel. By positioning and moving this voxel inside the resist, 3D manufacturing is possible. Therefore the technique can be used for the single step fabrication of a closed channel. By vertically moving the voxel through the resist, pores can be manufactured. In literature an ellipsoidal voxel shape is assumed, leading to the assumption that the maximum voxel, and therefore pore diameter is found at the focal plane, i.e. at z = 0. However, this research shows that the voxel may also have an hourglass-shape for a high enough laser intensity. In this case the maximum voxel diameter is found at a distance z from the focal plane. For the production of pores, therefore the maximum voxel diameter instead of the diameter at the focal plane has to be taken into account. The smallest pores produced measured 250 nm - 290 nm. AZ 4562 was used as a stamp and a mold for the manufacturing of 3D topographical features on a PDMS surface. Finally the microfluidic device was successfully produced in a layer of 50 µm thick resist. The channel width was 100 µm and the height was 10 µm. The channels were separated by 10 µm in height. The sizes of the input and output holes were adapted to the diameter of the smallest available blunt needle, which is 210 µm.
TL;DR: CT-number-Calibrated Diameter is an effective method to enhance the accuracy of the estimate of small vessel diameters and degree of coronary stenosis in CCTA.
Abstract: Author(s): Chen, Zhennong; Contijoch, Francisco; Schluchter, Andrew; Grady, Leo; Schaap, Michiel; Stayman, Web; Pack, Jed; McVeigh, Elliot | Abstract: PurposeCoronary x-ray computed tomography angiography (CCTA) continues to develop as a noninvasive method for the assessment of coronary vessel geometry and the identification of physiologically significant lesions. The uncertainty of quantitative lesion diameter measurement due to limited spatial resolution and vessel motion reduces the accuracy of CCTA diagnoses. In this paper, we introduce a new technique called computed tomography (CT)-number-Calibrated Diameter to improve the accuracy of the vessel and stenosis diameter measurements with CCTA.MethodsA calibration phantom containing cylindrical holes (diameters spanning from 0.8nmm through 4.0nmm) capturing the range of diameters found in human coronary vessels was three-dimensional printed. We also printed a human stenosis phantom with 17 tubular channels having the geometry of lesions derived from patient data. We acquired CT scans of the two phantoms with seven different imaging protocols. Calibration curves relating vessel intraluminal maximum voxel value (maximum CT number of a voxel, described in Hounsfield Units, HU) to true diameter, and full-width-at-half maximum (FWHM) to true diameter were constructed for each CCTA protocol. In addition, we acquired scans with a small constant motion (15nmm/s) and used a motion correction reconstruction (Snapshot Freeze) algorithm to correct motion artifacts. We applied our technique to measure the lesion diameter in the 17 lesions in the stenosis phantom and compared the performance of CT-number-Calibrated Diameter to the ground truth diameter and a FWHM estimate.ResultsIn all cases, vessel intraluminal maximum voxel value vs diameter was found to have a simple functional form based on the two-dimensional point spread function yielding a constant maximum voxel value region above a cutoff diameter, and a decreasing maximum voxel value vs decreasing diameter below a cutoff diameter. After normalization, focal spot size and reconstruction kernel were the principal determinants of cutoff diameter and the rate of maximum voxel value reduction vs decreasing diameter. The small constant motion had a significant effect on the CT number calibration; however, the motion-correction algorithm returned the maximum voxel value vs diameter curve to that of stationary vessels. The CT number Calibration technique showed better performance than FWHM estimation of diameter, yielding a high accuracy in the tested range (0.8nmm through 2.5nmm). We found a strong linear correlation between the smallest diameter in each of 17 lesions measured by CT-number-Calibrated Diameter (DC ) and ground truth diameter (Dgt ), (DC n=n0.951n×nDgt n+n0.023nmm, rn=n0.998 with a slope very close to 1.0 and intercept very close to 0nmm.ConclusionsComputed tomography-number-Calibrated Diameter is an effective method to enhance the accuracy of the estimate of small vessel diameters and degree of coronary stenosis in CCTA.