Extended Acquisition Time Research Articles

Optimization of 3D imaging time reduction by assessing spatial resolution in the slice selective direction using the ladder method

PurposeAssessing spatial resolution in MRI is challenging due to non-linearity. Despite the widespread use of 3D imaging in clinical practice for lesion detection and multi-planar reconstruction (MPR), the extended acquisition time poses a shortcoming. To address this, the “Slice resolution” parameter is utilized; however, its impact on MPR images is unclear. This study aims to assess spatial resolution using the ladder method, investigate the effects of diverse slice resolution settings in various imaging sequences, and propose optimal conditions. MethodsImages were acquired using various 3D imaging sequences—SPACE T1WI, SPACE T2WI, and VIBE T1WI—with different slice resolutions. Axial cross-section images were acquired and reconstructed into coronal cross-sections. The ladder method was employed for objective evaluation, including spatial frequency analysis. Additionally, visual evaluation was conducted and compared with ladder method results. ResultsFor three imaging sequences, the evaluated value of ladder method remained relatively constant from 100 % to 80 % slice resolution. However, the evaluated value decreased in low-spatial frequency for slice resolution below 70 %. ConclusionsResults from both ladder method and visual evaluations indicated image quality remained stable when the slice resolution was decreased to 80 %, potentially enabling a 20 % reduction in imaging time while preserving resolution in other cross-sections reconstructed by MPR.

Detecting element migration from ore systems: an LA-ICP-MS method for the in situ measurement of element contents and 207 Pb/ 206 Pb values on rough fracture coatings

In situ elemental content and 207 Pb/ 206 Pb values in three rough fracture coatings within drill cores from the McArthur River unconformity-related uranium deposit, Athabasca Basin, Canada, were measured using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) image mapping. Fracture-coating samples were located proximal and distal to the ore deposit. Samples required minimal preparation in this method, with areas ( c . 500 × 500 μ m) targeted in a cell-spaced grid pattern using a 50 μ m spot, spaced 200 μ m on the x -axis with an offset of 100 μ m on the y -axis, to overcome sample surface topography. A 5 s acquisition time was applied to elemental content measurements and a 2 s acquisition time was applied to 207 Pb/ 206 Pb measurements. These parameters increased the spatial resolution and analytical sensitivity and minimized the contribution of the host rock underlying the fracture surface to the geochemical signal in comparison to extended acquisition times. In addition, laser ablation temporal profiles allow for the interpretation of the timing of element/isotope migration and fixation on the rough fracture coating. Rasterized maps generated in Iolite™ v.4 demonstrate the chemical distribution of elements and 207 Pb/ 206 Pb values on the rough fracture coatings, allowing for the identification of mineral phases hosting pathfinder elements, pathfinder element associations and the generation of bulk in situ or specific mineralogy geochemical values. Bulk in situ values calculated using an integration of the 2D image data and targeting the c . 500 × 500 μ m surface of the fracture coating compared to previous bulk geochemical methods obtained by sampling the fracture coating with a microdrill (i.e. modified aqua regia (HCl: HNO 3 : H 2 O) and weak acid leach (2% HNO 3 )) highlights that in situ analysis greatly improved detection of pathfinder elements on the fracture surface. This study is the first application of in situ LA-ICP-MS for measuring element contents and 207 Pb/ 206 Pb values on rough fracture coatings and demonstrates its importance as a new geochemical tool to the mining industry for future mineral exploration.

Optimizing Low-Dose [18F]FDG-PET/CT Scans: Ensuring Quality Amid Radiotracer Availability Challenges – Insights from a Peripheral Tertiary Care Center

Background: The introduction of positron emission tomography/computed tomography (PET/CT) has significantly advanced medical imaging. In oncology, 18F-fluorodeoxyglucose (18F-FDG) PET/CT is particularly crucial for staging, evaluating treatment response, monitoring follow-up, and planning radiotherapy. However, in resource limiting hospitals, the availability of fluorine-labeled 18F-FDG limits optimal scan acquisition. This study aims to determine the optimal dosage and acquisition time to maximize patient throughput during shortages. Aim and Objective: To optimize low-dose 18F-FDG scan protocols while maintaining high image quality despite radiotracer availability challenges. Materials and Methods: PET/CT scans were performed using GE’s Discovery IQ 5-ring, 16-slice system within 40–60 minutes of intravenous 18F-FDG injection. The protocol was adjusted to a low-dose (0.05 mCi/kg of 18F-FDG), and the PET data acquisition time was increased to 3 min per bed position to ensure image quality. Results: Notable differences were observed in image quality scores based on varying acquisition times, with the extended acquisition time helping maintain diagnostic standards despite reduced tracer doses. Conclusion: The high sensitivity and long axial length of the PET/CT system (with five rings spanning 26 cm AFOV) can significantly alleviate the challenges faced by cyclotron-dependent centers. By leveraging the increased sensitivity, we successfully reduced the injected activity rather than the scan time to address the tracer shortage at our institute. This approach proved to be effective in maintaining image quality and patient care standards.

Room-temperature phosphorescence of defect-engineered silica nanoparticles for high-contrast afterglow bioimaging

Room-temperature phosphorescence (RTP) has tremendous potential in optics and photonics. Unlike fluorescence, RTP has substantial afterglow signals even after the excitation light is removed, which allows for extended acquisition times and higher signal-to-noise ratio under time-gated bioimaging. However, conventional RTP materials, both metal-containing and metal-free organic compounds, typically have limited photostability and inherent toxicity, making them unsuitable for long-term biological applications. Here, we report metal- and organic fluorophore-free silica nanoparticles (SNPs) that facilitate long-lived phosphorescence and exhibit RTP for high-contrast bioimaging. Polycondensation of silicon precursors and silyl biphenyls forms biphenyl-doped SNPs (bSNPs), and thermal decomposition of biphenyl moieties generates optically active defects in the biphenyl-bonded silicate network. The calcined bSNPs (C-bSNPs) have RTP-related biphenyl defects composed of carbon impurities, corresponding to spectroscopic measurements and ab initio calculations. Facile surface functionalization of defect-engineered C-bSNPs with tumor-targeting peptides while maintaining long-lived RTP allows for tissue autofluorescence-free in vivo bioimaging for cancer diagnosis, surpassing the limitations of continuous-wave imaging.

Deep-learning-based reconstruction of undersampled MRI to reduce scan times: a multicentre, retrospective, cohort study

The extended acquisition times required for MRI limit its availability in resource-constrained settings. Consequently, accelerating MRI by undersampling k-space data, which is necessary to reconstruct an image, has been a long-standing but important challenge. We aimed to develop a deep convolutional neural network (dCNN) optimisation method for MRI reconstruction and to reduce scan times and evaluate its effect on image quality and accuracy of oncological imaging biomarkers. In this multicentre, retrospective, cohort study, MRI data from patients with glioblastoma treated at Heidelberg University Hospital (775 patients and 775 examinations) and from the phase 2 CORE trial (260 patients, 1083 examinations, and 58 institutions) and the phase 3 CENTRIC trial (505 patients, 3147 examinations, and 139 institutions) were used to develop, train, and test dCNN for reconstructing MRI from highly undersampled single-coil k-space data with various acceleration rates (R=2, 4, 6, 8, 10, and 15). Independent testing was performed with MRIs from the phase 2/3 EORTC-26101 trial (528 patients with glioblastoma, 1974 examinations, and 32 institutions). The similarity between undersampled dCNN-reconstructed and original MRIs was quantified with various image quality metrics, including structural similarity index measure (SSIM) and the accuracy of undersampled dCNN-reconstructed MRI on downstream radiological assessment of imaging biomarkers in oncology (automated artificial intelligence-based quantification of tumour burden and treatment response) was performed in the EORTC-26101 test dataset. The public NYU Langone Health fastMRI brain test dataset (558 patients and 558 examinations) was used to validate the generalisability and robustness of the dCNN for reconstructing MRIs from available multi-coil (parallel imaging) k-space data. In the EORTC-26101 test dataset, the median SSIM of undersampled dCNN-reconstructed MRI ranged from 0·88 to 0·99 across different acceleration rates, with 0·92 (95% CI 0·92-0·93) for 10-times acceleration (R=10). The 10-times undersampled dCNN-reconstructed MRI yielded excellent agreement with original MRI when assessing volumes of contrast-enhancing tumour (median DICE for spatial agreement of 0·89 [95% CI 0·88 to 0·89]; median volume difference of 0·01 cm3 [95% CI 0·00 to 0·03] equalling 0·21%; p=0·0036 for equivalence) or non-enhancing tumour or oedema (median DICE of 0·94 [95% CI 0·94 to 0·95]; median volume difference of -0·79 cm3 [95% CI -0·87 to -0·72] equalling -1·77%; p=0·023 for equivalence) in the EORTC-26101 test dataset. Automated volumetric tumour response assessment in the EORTC-26101 test dataset yielded an identical median time to progression of 4·27 months (95% CI 4·14 to 4·57) when using 10-times-undersampled dCNN-reconstructed or original MRI (log-rank p=0·80) and agreement in the time to progression in 374 (95·2%) of 393 patients with data. The dCNN generalised well to the fastMRI brain dataset, with significant improvements in the median SSIM when using multi-coil compared with single-coil k-space data (p<0·0001). Deep-learning-based reconstruction of undersampled MRI allows for a substantial reduction of scan times, with a 10-times acceleration demonstrating excellent image quality while preserving the accuracy of derived imaging biomarkers for the assessment of oncological treatment response. Our developments are available as open source software and hold considerable promise for increasing the accessibility to MRI, pending further prospective validation. Deutsche Forschungsgemeinschaft (German Research Foundation) and an Else Kröner Clinician Scientist Endowed Professorship by the Else Kröner Fresenius Foundation.

Probing the Cellular Fate of the Protein Corona around Nanoparticles with Nanofocused X-ray Fluorescence Imaging.

X-ray fluorescence imaging (XRF-imaging) with subcellular resolution is used to study the intracellular integrity of a protein corona that was pre-formed around gold nanoparticles (AuNP). Artificial proteins engineered to obtain Gd coordination for detection by XRF-imaging were used to form the corona. Indications about the degradation of this protein corona at a cellular and subcellular level can be observed by following the Au and Gd quantities in a time and spatial-dependent manner. The extended acquisition times necessary for capturing individual XRF-imaging cell images result in relatively small sample populations, stressing the need for faster image acquisition strategies in future XRF-imaging-based studies to deal with the inherent variability between cells. Still, results obtained reveal degradation of the protein corona during cellular trafficking, followed by differential cellular processing for AuNP and Gd-labelled proteins. Overall, this demonstrates that the dynamic degradation of the protein corona can be tracked by XRF-imaging to a certain degree.

Investigation of Equivalence Between Non-Resonant Raman Excitation Spectroscopy and Conventional Raman Spectroscopy

As spontaneous Raman spectroscopy is demonstrated to be viable for many applications, it is still held back by its inherently low signal and typically extended acquisition time. While several techniques can overcome this by enhancing the scattered signal to quicken acquisition, a parallel field that quickens spectral acquisition using instrumentation has received less focus. In principle, Raman spectra could be obtained by tuning the excitation wavelength and measuring the Raman signal at a fixed wavelength using a single-pixel detector. Before exploring the potential of quicker acquisition, it is important to first study the equivalence of Raman Excitation Spectroscopy and conventional Raman Spectroscopy experimentally. We demonstrate the equivalence between the two techniques for biological and non-biological samples by measuring Raman Excitation Maps. Additionally, we explore the interpolation of low-resolution excitation spectra using excess information in the maps for higher resolution excitation spectra. This work, together with current progression in fast tunable lasers and highly sensitive single-pixel detectors, provides a promising prospect for dedicated Raman Excitation Spectroscopy instruments to be developed.

Deep progressive learning achieves whole-body low-dose 18F-FDG PET imaging

ObjectivesTo validate a total-body PET-guided deep progressive learning reconstruction method (DPR) for low-dose 18F-FDG PET imaging.MethodsList-mode data from the retrospective study (n = 26) were rebinned into short-duration scans and reconstructed with DPR. The standard uptake value (SUV) and tumor-to-liver ratio (TLR) in lesions and coefficient of variation (COV) in the liver in the DPR images were compared to the reference (OSEM images with full-duration data). In the prospective study, another 41 patients were injected with 1/3 of the activity based on the retrospective results. The DPR images (DPR_1/3(p)) were generated and compared with the reference (OSEM images with extended acquisition time). The SUV and COV were evaluated in three selected organs: liver, blood pool and muscle. Quantitative analyses were performed with lesion SUV and TLR, furthermore on small lesions (≤ 10 mm in diameter). Additionally, a 5-point Likert scale visual analysis was performed on the following perspectives: contrast, noise and diagnostic confidence.ResultsIn the retrospective study, the DPR with one-third duration can maintain the image quality as the reference. In the prospective study, good agreement among the SUVs was observed in all selected organs. The quantitative results showed that there was no significant difference in COV between the DPR_1/3(p) group and the reference, while the visual analysis showed no significant differences in image contrast, noise and diagnostic confidence. The lesion SUVs and TLRs in the DPR_1/3(p) group were significantly enhanced compared with the reference, even for small lesions.ConclusionsThe proposed DPR method can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment while maintaining image quality.

Fatigue Effects on the Lower Leg Muscle Architecture Using Diffusion Tensor MRI

Proton density (PD) and diffusion tensor imaging (DTI) are imaging techniques that enable the acquisition of data from living subjects that can be used in the fine-tuning of subject-specific models’ architectural parameters. The aim of this study was to determine the in vivo 3D architectural parameters (volume, pennation angle, fiber length and physiological cross-sectional area) of the gastrocnemius medialis, gastrocnemius lateralis, soleus and tibialis anterior muscles using proton density and diffusion tensor imaging data before and after an exhaustive one-legged jump exercise. These methods were used in the in vivo 3D data acquisition of six young and physically active female subjects’ lower legs, followed by a fiber-tracking algorithm and analysis tools. No significant differences were found in the muscles’ architecture after the exercise, with the following exceptions: the anatomical cross-section area of the gastrocnemius medialis increased (p-value 0.001, effect size 0.18) after exercise; the fiber lengths of the gastrocnemius medialis, lateralis and soleus muscles were higher after exercise (p-value 0.002, 0.001 and 0.001, respectively, and effect size 2.03, 1.29 and 0.85, respectively); and the soleus mean pennation angle decreased after exercise (p-value 0.0015, effect size 2.31). These changes (or lack thereof) could be attributed to the extended acquisition time of the MRI scans to minimize noise: by increasing the acquisition time, the effect of the exercise may have been partially lost due to muscle recovery.

Simultaneous Multicolor DNA-PAINT without Sequential Fluid Exchange Using Spectral Demixing.

Several variants of multicolor single-molecule localization microscopy (SMLM) have been developed to resolve the spatial relationship of nanoscale structures in biological samples. The oligonucleotide-based SMLM approach “DNA-PAINT” robustly achieves nanometer localization precision and can be used to count binding sites within nanostructures. However, multicolor DNA-PAINT has primarily been realized by “Exchange-PAINT”, which requires sequential exchange of the imaging solution and thus leads to extended acquisition times. To alleviate the need for fluid exchange and to speed up the acquisition of current multichannel DNA-PAINT, we here present a novel approach that combines DNA-PAINT with simultaneous multicolor acquisition using spectral demixing (SD). By using newly designed probes and a novel multichannel registration procedure, we achieve simultaneous multicolor SD-DNA-PAINT with minimal crosstalk. We demonstrate high localization precision (3–6 nm) and multicolor registration of dual- and triple-color SD-DNA-PAINT by resolving patterns on DNA origami nanostructures and cellular structures.

Accelerating quantitative 13C NMR spectra using an EXtended ACquisition Time (EXACT) method.

Accurate quantitative 13C NMR spectra can be accelerated by using EXACT (EXtended ACquisition Time) NMR methods which reduce Nuclear Overhauser Enhancement (NOE) during the FID. This allows 30-50% shorter experiment times to be used when achieving a given level of quantitative accuracy.

MR method for measuring microscopic histologic soft tissue textures.

Provide a direct, non-invasive diagnostic measure of microscopic tissue texture in the size scale between tens of microns and the much larger scale measurable by clinical imaging. This paper presents a method and data demonstrating the ability to measure these microscopic pathologic tissue textures (histology) in the presence of subject motion in an MR scanner. This size range is vital to diagnosing a wide range of diseases. MR micro-Texture (MRµT) resolves these textures by a combination of measuring a targeted set of k-values to characterize texture-as in diffraction analysis of materials, performing a selective internal excitation to isolate a volume of interest (VOI), applying a high k-value phase encode to the excited spins in the VOI, and acquiring each individual k-value data point in a single excitation-providing motion immunity and extended acquisition time for maximizing signal-to-noise ratio. Additional k-value measurements from the same tissue can be made to characterize the tissue texture in the VOI-there is no need for these additional measurements to be spatially coherent as there is no image to be reconstructed. This method was applied to phantoms and tissue specimens including human prostate tissue. Data demonstrating resolution <50 µm, motion immunity, and clearly differentiating between normal and cancerous tissue textures are presented. The data reveal textural differences not resolvable by standard MR imaging. As MRµT is a pulse sequence, it is directly translatable to MRI scanners currently in clinical practice to meet the need for further improvement in cancer imaging.

Respiratory Gating and the Performance of PET/CT in Pulmonary Lesions.

BackgroundMotion artifacts related to the patient’s breathing can be the cause of underestimation of the lesion uptake and can lead to missing of small lung lesions. The respiratory gating (RG) technology has demonstrated a significant increase in image quality.ObjectiveThe aim of this paper was to evaluate the advantages of RG technique on PET/CT performance in lung lesions. The impact of 4D-PET/CT on diagnosis (metabolic characterization), staging and re-staging lung cancer was also assessed, including its application for radiotherapy planning. Finally, new technologies for respiratory motion management were also discussed.MethodsA comprehensive electronic search of the literature was performed by using Medline database (PubMed) searching “PET/CT”, “gated” and “lung”. Original articles, review articles, and editorials published in the last 10 years were selected, included and critically reviewed in order to select relevant articles.ResultsMany papers compared Standardized Uptake Value (SUV) in gated and ungated PET studies showing an increase in SUV of gated images, particularly for the small lesions located in medium and lower lung. In addition, other features as Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and textural-features presented differences when obtained from gated and ungated PET acquisitions. Besides the increase in quantification, gating techniques can determine an increase in the diagnostic accuracy of PET/CT. Gated PET/CT was evaluated for lung cancer staging, therapy response assessment and for radiation therapy planning.ConclusionNew technologies able to track the motion of organs lesion directly from raw PET data, can reduce or definitively solve problems (i.e.: extended acquisition time, radiation exposure) currently limiting the use of gated PET/CT in clinical routine.

Measurements of cerebral blood volume using quantitative susceptibility mapping, R2 * relaxometry, and ferumoxytol-enhanced MRI.

Ferumoxytol-enhanced MRI holds potential for the non-invasive assessment of vascular architecture using estimates of cerebral blood volume (CBV). Ferumoxytol specifically enables steady-state imaging with extended acquisition times, for substantial improvements in resolution and contrast-to-noise ratio. With such data, quantitative susceptibility mapping (QSM) can be used to obtain images of local tissue magnetic susceptibility and hence estimate the increase in blood susceptibility after administration of a contrast agent, which in turn can be correlated to tissue CBV. Here, we explore the use of QSM for CBV estimation and compare it with R2 * (1/T2 *)-based results. Institutional review board approval was obtained, and all subjects provided written informed consent. For this prospective study, MR images were acquired on a 3.0T scanner in 19 healthy subjects using a multiple-echo T2 *-weighted sequence. Scanning was performed before and after the administration of two doses of ferumoxytol (1mg FE/kg and 4mg FE/kg). Different QSM approaches were tested on numerical phantom simulations. Results showed that the accuracy of magnetic susceptibility measurements improved with increasing image resolution and decreasing vascular density. In vivo changes in magnetic susceptibility were measured after the administration of ferumoxytol utilizing QSM, and significantly higher QSM-based CBV was measured in gray matter compared with white matter. QSM- and R2 *-based CBV estimates correlated well, with similar average values, but a larger variance was found in QSM-based estimates.

Hierarchical spiral-scan trajectory for efficient scanning ion conductance microscopy

Scanning ion conductance microscopy (SICM) is an emerging technique for non-contact, high-resolution topography imaging, especially suitable for live cells investigation in a physiological environment. Despite its rapid development, the extended acquisition time issues of its typical hopping/backstep scanning mode still restrict its application for more fields. Herein, we propose a novel SICM scanning approach to effectively reduce the retract distance of existing hopping/backstep mode. In this approach, the SICM probe first gradually descends in the z-direction. Then by using Archimedes spiral trajectory, which has the advantage of higher angular velocity due to its continuous and smooth trajectory, the probe rapidly detects the highest point of the sample in the xy-plane in a layer-by-layer way. Further, the maximum height that decides the retrace distance of pipet in the detected region can be quickly achieved, avoiding a huge retrace distance usually adopted in the existing methods without any prior knowledge (sample height and steepness in the scanning region). Therefore, this new scanning method can greatly reduce the imaging time by minimizing the retrace height of each measurement point. Theoretical analysis is conducted to compare the imaging time of traditional and new method. And various factors in the new method that affect the imaging speed are analyzed. In addition, PDMS (polydimethylsiloxane) and biological samples (C2C12 cells) were imaged by SICM that was operated in the hopping mode, raster-based detecting and developed method with a single-barrel pipet, respectively. The experimental results suggest that the new method has a faster imaging speed than conventional scanning modes but does not sacrifice the imaging quality.

Intensity calibration and sensitivity factors for XPS instruments with monochromatic Ag Lα and Al Kα sources

This paper provides a description of the transmission function of an X‐ray photoelectron spectroscopy (XPS) instrument operating with exchangeable Al Kα (1486.6 eV) and Ag Lα (2984.3 eV) sources. Both sources use the same quartz crystal monochromator and illuminate the same area of the sample. The transmission‐function–corrected data from sputter cleaned gold provides a useful reference material to calibrate other instruments of the same type. Sensitivity factors for Ag Lα and Al Kα are calculated from photoionisation cross sections and electron effective attenuation lengths. These compare well with previous experimental values and data acquired from ionic liquids. The intensity of the Ag Lα source is found to be approximately 50 times lower than the Al Kα source. This, coupled with generally lower photoemission efficiencies, results in noisier data or extended acquisition times. However, there are clear advantages to using the Ag Lα source to analyse certain elements where additional core levels can be accessed and for many technologically important elements where interference from Auger electron peaks can be eliminated. The combination of calibrated data from both sources provides direct and easily interpreted insight into the depth distribution of chemical species. This could be particularly important for topographic samples, where angle resolved experiments are not always helpful. We also demonstrate, using thin coatings of chromium and carbon, that the inelastic background in Ag Lα wide‐scan spectra has a significantly increased information depth compared with Al Kα.

A feasibility study on the use of MV-CBCT images for urgent palliative treatment planning

Introduction: The application of 3D volumetric imaging modalities in treatment planning of radiation therapy can provide more precisely define tumor localization, and computed tomography (CT) is the most common accepted method for treatment planning. Given the lack of a CT scanner stationed in all radiotherapy departments and equipping most of the medical linear accelerators with only electronics portal imaging device (EPID) device, the use of this technology for megavoltage cone-beam computed tomography (MV-CBCT) imaging in such cases as urgent palliative radiotherapy treatments, leads to precise localization of the tumor and increases the accuracy of the beam sent to the target area. Since MV-CBCT imaging is possible using EPID, this study is aimed at conducting MV-CBCT and investigating the possibility of using these images in the treatment planning of the radiation therapy. Materials and Methods: Initially, the projection data of an anthropomorphic head phantom was acquired at 3o increments for a 360° of gantry rotation around the patient, and then the 2D projections were reconstructed with Feldkamp cone-beam algorithm. The intensity-to- electron-density calibration was performed for MV-CBCT images to converts the reconstructed gray-level intensity of each image voxel into an electron density value. The reconstructed MV-CBCT images were sent to the treatment planning software, and after the registration with KVCT images, two independent plans were generated on the both CT datasets. Finally, the dose volume histogram (DVH) of the anatomical targets contoured with MV-CBCT was compared to DVH of the same targets contoured with KVCT images. Results: There was a high level of agreement between the MV-CBCT and KVCT plans with the anatomical structures of the skull as the target. The shift between the co-ordinate positions of the anatomical points identified on the MV-CBCT from the reference planning CT points, and the calculated dose based on the both CT datasets have an acceptable level of agreement. Conclusion: The results of this study show that MV-CBCT images could be effective for treatment planning modality include single fraction palliative treatment. However, low contrast resolution and extended scan acquisition time are the two main limiting factor that eliminate this imaging modality only for palliative treatments at easily distinguishable area, such as brain.

A fast scanning ion conductance microscopy imaging method using compressive sensing and low-discrepancy sequences.

A scanning ion conductance microscope (SICM) is a multifunctional, high-resolution imaging technique whose non-contact nature makes it very suitable for imaging of biological samples such as living cells in a physiological environment. However, a drawback of hopping/backstep mode of SICM is its relatively slow imaging speed, which seriously restricts the study on the dynamic process of biological samples. This paper presents a new undersampled scanning method based on Compressed Sensing (CS-based scanning mode) theory to solve extended acquisition time issues in the hopping/backstep mode. Compressive sensing can break through the limit of the Nyquist sampling theorem and sample the original sparse/compressible signal at a rate lower than the Nyquist frequency. In the CS-based scanning mode, three sampling patterns, including the random sampling pattern and two kinds of sampling patterns produced by low-discrepancy sequences, were employed as the measurement locations to obtain the undersampled data with different undersampling ratios. Also TVAL3 (Total Variation Augmented Lagrangian ALternating-direction ALgorithm) was then utilized as a reconstruction algorithm to reconstruct the undersampled data. Compared with the nonuniform sampling points of random patterns at a low undersampling ratio, low-discrepancy sequences can produce a more uniform distribution point. Three types of samples with different complexity of topography were scanned by SICM using the conventional hopping/backstep mode and CS-based undersampled scanning mode. The comparisons of the imaging speed and quality with two scanning modes illustrate that the CS-based scanning mode can effectively speed up SICM imaging speed while not sacrificing the image quality. Also low-discrepancy sampling patterns can achieve a better reconstruction performance than that of the random sampling pattern under the same undersampling ratio.

Smart Scanning Ion-Conductance Microscopy Imaging Technique Using Horizontal Fast Scanning Method.

To solve extended acquisition time issues inherent in the conventional hopping-scanning mode of scanning ion-conductance microscopy (SICM), a new transverse-fast scanning mode (TFSM) is proposed. Because the transverse motion in SICM is not the detection direction and therefore presents no collision problem, it has the ability to move at high speed. In TSFM, the SICM probe gradually descends in the vertical/detection direction and rapidly scans in the transverse/nondetection direction. Further, the highest point that decides the hopping height of each scanning line can be quickly obtained. In conventional hopping mode, however, the hopping height is artificially set without a priori knowledge and is typically very large. Consequently, TFSM greatly improves the scanning speed of the SICM imaging system by effectively reducing the hopping height of each pixel. This study verifies the feasibility of this novel scanning method via theoretical analysis and experimental study, and compares the speed and quality of the scanning images obtained in the TFSM with that of the conventional hopping mode. The experimental results indicate that the TFSM method has a faster scanning speed than other SICM scanning methods while maintaining the quality of the images. Therefore, TFSM provides the possibility to quickly obtain high-resolution three-dimensional topographical images of extremely complex samples.

Frequency-Modulated Continuous Flow Analysis Electrospray Ionization Mass Spectrometry (FM-CFA-ESI-MS) for Sample Multiplexing.

A method for multiplexed sample analysis by mass spectrometry without the need for chemical tagging is presented. In this new method, each sample is pulsed at unique frequencies, mixed, and delivered to the mass spectrometer while maintaining a constant total flow rate. Reconstructed ion currents are then a time-dependent signal consisting of the sum of the ion currents from the various samples. Spectral deconvolution of each reconstructed ion current reveals the identity of each sample, encoded by its unique frequency, and its concentration encoded by the peak height in the frequency domain. This technique is different from other approaches that have been described, which have used modulation techniques to increase the signal-to-noise ratio of a single sample. As proof of concept of this new method, two samples containing up to 9 analytes were multiplexed. The linear dynamic range of the calibration curve was increased with extended acquisition times of the experiment and longer oscillation periods of the samples. Because of the combination of the samples, salt had little effect on the ability of this method to achieve relative quantitation. Continued development of this method is expected to allow for increased numbers of samples that can be multiplexed.