The aim was to study the performance of the U-SPECT
/CT E-class system for preclinical imaging, to later demonstrate the viability of simultaneous multi-animal and multi-isotope imaging with reliable ...quantitative accuracy. The performance of the SPECT was evaluated for two collimators dedicated for mouse (UHS-M) and rat imaging (UHR-RM) in terms of sensitivity, energy resolution, uniformity and spatial resolution. Point sources, hot‑rod and uniform phantoms were scanned, and additional tests were carried out to evaluate singular settings such as simultaneous multi-isotope acquisition and imaging with a multi-bed system. For in-vivo evaluation, simultaneous triple-isotope and multi-animal studies were performed on mice. Sensitivity for
Tc was 2370 cps/MBq for the UHS-M collimator and 493 cps/MBq for the UHR-RM. Rods of 0.6 mm and 0.9 mm were discernible with the UHS-M and UHR-RM collimators respectively, with optimized reconstruction. Uniformity in low counting conditions has proven to be poor (> 75%). Multi-isotope and multi-bed phantom acquisitions demonstrated accurate quantification. In mice, simultaneous multi-isotope imaging provided the separate distribution of 3 tracers and image quality of the multi-mouse bone scan was adequate. The U-SPECT
/CT E-class has shown good sensitivity and spatial resolution. This system provides quantitative images with suitable image quality for multi-mouse and multi-isotope acquisitions.
Radioembolization (RE) with yttrium-90 (
Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to ...correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six
Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by
Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual
Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict
Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.
Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the ...reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-11C- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the ...association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers.
We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification.
Eighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval CI = 0.779-0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100).
Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer's disease.
Background
The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.
PET/CT ...studies of 210 patients were reviewed including Torso (
n
= 123), Whole body (WB) (
n
= 36), Head and Neck Tumor (HNT) (
n
= 10), and Brain (
n
= 41) protocols with
18
FDG (
n
= 170),
11
C-CHOL (
n
= 10),
18
FDOPA (
n
= 10),
11
C-MET (
n
= 10), and
18
F-florbetapir (
n
= 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product.
Results
Total ED (mean ± SD) for Torso-
11
C-CHOL, Torso-
18
FDG, WB-
18
FDG, and HNT-
18
FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For
18
FDG,
18
FDOPA,
11
C-MET, and
18
F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In
18
FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (
p
< 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv.
Conclusions
The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.
Therapies consisting of a combination of agents are an attractive proposition, especially in the context of diseases such as cancer, which can manifest with a variety of tumor types in a single case. ...However uncovering usable drug combinations is expensive both financially and temporally. By employing computational methods to identify candidate combinations with a greater likelihood of success we can avoid these problems, even when the amount of data is prohibitively large. Hitting Set is a combinatorial problem that has useful application across many fields, however as it is NP-complete it is traditionally considered hard to solve exactly. We introduce a more general version of the problem (α,β,d)-Hitting Set, which allows more precise control over how and what the hitting set targets. Employing the framework of Parameterized Complexity we show that despite being NP-complete, the (α,β,d)-Hitting Set problem is fixed-parameter tractable with a kernel of size O(αdk(d)) when we parameterize by the size k of the hitting set and the maximum number α of the minimum number of hits, and taking the maximum degree d of the target sets as a constant. We demonstrate the application of this problem to multiple drug selection for cancer therapy, showing the flexibility of the problem in tailoring such drug sets. The fixed-parameter tractability result indicates that for low values of the parameters the problem can be solved quickly using exact methods. We also demonstrate that the problem is indeed practical, with computation times on the order of 5 seconds, as compared to previous Hitting Set applications using the same dataset which exhibited times on the order of 1 day, even with relatively relaxed notions for what constitutes a low value for the parameters. Furthermore the existence of a kernelization for (α,β,d)-Hitting Set indicates that the problem is readily scalable to large datasets.
Abstract Carbon-11 labeled dihydrotetrabenazine (11 C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with ...Parkinson's disease. Here, we applied11 C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site.11 C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new11 C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT).11 C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between11 C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p < 0.001). The data presented here indicate that11 C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.
Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment than amyloid deposition, is currently gauged by the degree of regional atrophy. However, functional markers, such as ...GABA(A) receptor density, a marker of neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A) messenger RNA expression is reduced even in mild cognitive impairment. We measured whole-brain GABA(A) binding potential in vivo using (11)C-flumazenil positron emission tomography and compared GABA(A) binding with metabolic and volumetric measurements. For this purpose, we studied 12 subjects, six patients with early Alzheimer's disease and six healthy controls, with (11)C-flumazenil and (18)F-fluorodeoxyglucose positron emission tomography, as well as with high-resolution magnetic resonance imaging. Data were evaluated with both voxel-based parametric methods and volume of interest methods. We found that in early Alzheimer's disease, with voxel-based analysis, (11)C-flumazenil binding was decreased in infero-medial temporal cortex, retrosplenial cortex and posterior perisylvian regions. Inter-group differences reached corrected significance when using an arterial input function. Metabolism measured with positron emission tomography and volumetric measurements obtained with magnetic resonance imaging showed changes in regions affected in early Alzheimer's disease, but, unlike with (11)C-flumazenil binding and probably due to sample size, the voxel-based findings failed to reach corrected significance in any region of the brain. With volume of interest analysis, hippocampi and posterior cingulate gyrus showed decreased (11)C-flumazenil binding. In addition, (11)C-flumazenil hippocampal binding correlated with memory performance. Remarkably, (11)C-flumazenil binding was decreased precisely in the regions showing the greatest degree of neuronal loss in post-mortem studies of early Alzheimer's disease. From these data, we conclude that (11)C-flumazenil binding could be a useful marker of neuronal loss in early Alzheimer's disease.
Perceived prescription for multifocal contact lenses Raso, Alicia López; Alonso, Jose Manuel Lopez; Alcocer, Javier Ruiz ...
Acta ophthalmologica (Oxford, England),
December 2022, 2022-12-00, 20221201, Volume:
100, Issue:
S275
Journal Article
Peer reviewed
Purpose: Multifocal contact lenses have a variable power map that is typically radial. The prescription of these lenses is given as a Sphere plus Addition values in diopters. They are calculated by ...assigning different radial rings of the lens to different mean power values (near and far vision zones). Depth of focus (DOF) should be high in order to focus both images on the retina. This calculation usually depends on each manufacturer and design type. The purpose of this work is to give a simple common criterion for perceived prescription, based on visual criteria and patient's pupil.
Methods: The radial power profile of different multifocal contact lens designs was measured with a NIMO TR1504 (Lambda‐X). Using geometrical optics and MATLAB, ray tracing is performed and the position of the smallest spot size plane, noted as Df, is recorded. Spot size in that plane is recorded too. From Df, graphs of perceived diopters (inverse of Df in meters) versus different diameter portions of the lens are obtained.
Results: The method provides the sphere and addition values for lenses with zonal designs based on the maximum and minimum effective power seen by the patient as a function of pupil size. The main perceived diopter grows or decrease smoothly depending on centre‐near or centre‐distance designs. The calculation of the approximate size of the spot with the diameter also allows estimating the DOF too. In Extended Depth of Focus (EDOF) lenses the method is also applicable without changes of criteria.
Conclusions: The determination of the prescription perceived by the patient with multifocal contact lenses is important and there are no uniform methods for the different designs. The inclusion of the diameter used by each patient allows the inclusion of visual criteria for calculation of main perceived diopter and the use of a common method.
Purpose: Spherical multifocal contact lenses are typically designed with a rotationally symmetrical power profile. Imperfections in the raw material, manufacturing and measurement process can break ...this symmetry, altering the intended lens design. The purpose of this work is to develop a method to separate the intended symmetric design profile from the asymmetries and to give the spatial distribution of the measurement noise uncertainty in diopters.
Methods: NIMO TR1504 (Lambda‐X) version V.2.13.2 has been used to measure the local power map of various multifocal contact lenses. From the map, a set of radial power profiles is obtained for different angles (0°, 180°), (0°, 360°). A symmetrical lens should show a constant radial profile for different angles, while asymmetries manifest as differences in the set of radial power profiles. They are analysed using a Principal Components Method (PCA) implemented in MATLAB.
Results: The method displays a map of the symmetric radial profile of the lens, another map of the deviations with spatial structure indicating the angles where the deviations are stronger (rotational asymmetries), and noise with three separated components (spatially random variations). Asymmetries of the order of 0.17D (with maximums of 0.4D), and random noise values of 0.12D were found in some lenses.
Conclusions: The characterization of multifocal contact lens prescription is important in visual optics. The prescription perceived by the patient depends on the distribution of the radial power profile on the pupil. That is the reason why asymmetries and imperfections estimation is important. The method developed in this work allows to calculate a diopter equivalent number for them.
PDF
