Computed Imaging Techniques Research Articles

Can We Improve Antifungal Susceptibility Testing?

Systemic antifungal agents are increasingly used for prevention or treatment of invasive fungal infections, whose prognosis remains poor. At the same time, emergence of resistant or even multi-resistant strains is of concern as the antifungal arsenal is limited. Antifungal susceptibility testing (AFST) is therefore of key importance for patient management and antifungal stewardship. Current AFST methods, including reference and commercial types, are based on growth inhibition in the presence of an antifungal, in liquid or solid media. They usually enable Minimal Inhibitory Concentrations (MIC) to be determined with direct clinical application. However, they are limited by a high turnaround time (TAT). Several innovative methods are currently under development to improve AFST. Techniques based on MALDI-TOF are promising with short TAT, but still need extensive clinical validation. Flow cytometry and computed imaging techniques detecting cellular responses to antifungal stress other than growth inhibition are also of interest. Finally, molecular detection of mutations associated with antifungal resistance is an intriguing alternative to standard AFST, already used in routine microbiology labs for detection of azole resistance in Aspergillus and even directly from samples. It is still restricted to known mutations. The development of Next Generation Sequencing (NGS) and whole-genome approaches may overcome this limitation in the near future. While promising approaches are under development, they are not perfect and the ideal AFST technique (user-friendly, reproducible, low-cost, fast and accurate) still needs to be set up routinely in clinical laboratories.

Templating of Syndesmotic Ankle Lesions by Use of 3D Analysis in Weightbearing and Nonweightbearing CT.

Diagnosis and operative treatment of syndesmotic ankle injuries remain challenging due to the limitations of 2-dimensional imaging. The aim of this study was therefore to develop a reproducible method to quantify the displacement of a syndesmotic lesion based on 3-dimensional computed imaging techniques. Eighteen patients with a unilateral syndesmotic lesion were included. Bilateral imaging was performed with weightbearing cone-beam computed tomography (CT) in case of a high ankle sprain (n = 12) and by nonweightbearing CT in case of a fracture-associated syndesmotic lesion (n = 6). The healthy ankle was used as a template after being mirrored and superimposed on the contralateral ankle. The following anatomical landmarks of the distal fibula were computed: the most lateral aspect of the lateral malleolus and the anterior and posterior tubercle. The change in position of these landmarks relative to the stationary, healthy fibula was used to quantify the syndesmotic lesion. A control group of 7 studies was used. The main clinical relevant findings demonstrated a statistically significant difference between the mean mediolateral diastasis of both the sprained (mean [SD], 1.6 [1.0] mm) and the fracture group (mean [SD], 1.7 [0.6] mm) compared to the control group ( P < .001). The mean external rotation was statistically different when comparing the sprained (mean [SD], 4.7 [2.7] degrees) and the fracture group (mean [SD], 7.0 [7.1] degrees) to the control group ( P < .05). This study evaluated an effective method for quantifying a unilateral syndesmotic lesion of the ankle. Applications in clinical practice could improve diagnostic accuracy and potentially aid in preoperative planning by determining which correction needs to be achieved to have the fibula correctly reduced in the syndesmosis. Level III, retrospective comparative study.

Interferometric synthetic aperture microscopy for extended focus optical coherence microscopy.

Optical coherence microscopy (OCM) is an interferometric technique providing 3D images of biological samples with micrometric resolution and penetration depth of several hundreds of micrometers. OCM differs from optical coherence tomography (OCT) in that it uses a high numerical aperture (NA) objective to achieve high lateral resolution. However, the high NA also reduces the depth-of-field (DOF), scaling with 1/NA2. Interferometric synthetic aperture microscopy (ISAM) is a computed imaging technique providing a solution to this trade-off between resolution and DOF. An alternative hardware method to achieve an extended DOF is to use a non-Gaussian illumination. Extended focus OCM (xfOCM) uses a Bessel beam to obtain a narrow and extended illumination volume. xfOCM detects back-scattered light using a Gaussian mode in order to maintain good sensitivity. However, the Gaussian detection mode limits the DOF. In this work, we present extended ISAM (xISAM), a method combining the benefits of both ISAM and xfOCM. xISAM uses the 3D coherent transfer function (CTF) to generalize the ISAM algorithm to different system configurations. We demonstrate xISAM both on simulated and experimental data, showing that xISAM attains a combination of high transverse resolution and extended DOF which has so far been unobtainable through conventional ISAM or xfOCM individually.

Computed optical interferometric tomography for high-speed volumetric cellular imaging.

Three-dimensional high-resolution imaging methods are important for cellular-level research. Optical coherence microscopy (OCM) is a low-coherence-based interferometry technology for cellular imaging with both high axial and lateral resolution. Using a high-numerical-aperture objective, OCM normally has a shallow depth of field and requires scanning the focus through the entire region of interest to perform volumetric imaging. With a higher-numerical-aperture objective, the image quality of OCM is affected by and more sensitive to aberrations. Interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO) are computed imaging techniques that overcome the depth-of-field limitation and the effect of optical aberrations in optical coherence tomography (OCT), respectively. In this work we combine OCM with ISAM and CAO to achieve high-speed volumetric cellular imaging. Experimental imaging results of ex vivo human breast tissue, ex vivo mouse brain tissue, in vitro fibroblast cells in 3D scaffolds, and in vivo human skin demonstrate the significant potential of this technique for high-speed volumetric cellular imaging.

Abstract P2-03-11: In situ imaging of the tumor cavity during breast lumpectomy using optical coherence tomography

Abstract Re-operation rates for breast lumpectomy procedures are exceedingly high, often over 30%, depending on the institution and surgical technique. Because current standard-of-care relies on post-operative histopathology to provide a microscopic view and assessment of surgical margins, there has been great interest in developing new imaging solutions to visualize tissues intraoperatively with high-resolution, and provide real-time feedback on the margin status. While it is possible to use a variety of microscopic imaging methods in the operating suite, including frozen-section histology, touch-prep cytology, confocal or scattering-based microscopy, all these techniques are limited to visualizing margins on ex vivo resected specimens, and do not provide a means for visualizing the in situ tumor cavity for evidence of positive margins or residual disease. Optical coherence tomography (OCT) is a high-resolution, real-time, optical biomedical imaging technology that is the optical analogue to ultrasound imaging, except images are based on backscattered near-infrared light. OCT is capable of performing optical biopsies of in situ tissue at resolutions that approach those in histopathology. With the use of an advanced computed imaging technique called ISAM (Interferometric Synthetic Aperture Microscopy), even higher imaging resolution over larger depths is possible, commensurate with the depths (1-2 mm) visualized by pathologists to determine negative, close, or positive margins. Past studies by our group and others have demonstrated the feasibility of intraoperative OCT for assessing tumor margin and lymph node status during breast cancer surgery, but to date, all studies have been performed on resected lumpectomy tissue. In this study, we report the development of a novel handheld surgical imaging probe that enables 2-D and 3-D OCT/ISAM imaging of the in situ tumor cavity, in addition to the margins of excised specimens. To date, this handheld OCT/ISAM probe has been used in 10 breast cancer surgeries where both in situ and ex vivo imaging was performed. Four of these cases involved in situ imaging of the cavity margin after a suspicious area was visually and tactically identified, and was subsequently resected, followed by ex vivo imaging and validating post-operative histopathology. Representative cases included fibroadipose tissue, fibroadenomas, and high-grade ductal carcinoma in situ. Distinct microstructural features identified on OCT/ISAM and confirmed with histopathology demonstrate that this technique can visualize the in situ tumor cavity, as well as the surgical margins on resected specimens, with micron-scale resolution. OCT/ISAM has the potential to determine margin status in real-time during the surgical procedure, when further surgical resection to establish clear margins and reduce re-operation rates is possible. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-11.

Real-time in vivo computed optical interferometric tomography

High-resolution real-time tomography of scattering tissues is important for many areas of medicine and biology1–6. However, the compromise between transverse resolution and depth-of-field in addition to low sensitivity deep in tissue continue to impede progress towards cellular-level volumetric tomography. Computed imaging has the potential to solve these long-standing limitations. Interferometric synthetic aperture microscopy (ISAM)7–9 is a computed imaging technique enabling high-resolution volumetric tomography with spatially invariant resolution. However, its potential for clinical diagnostics remains largely untapped since full volume reconstructions required lengthy postprocessing, and the phase-stability requirements have been difficult to satisfy in vivo. Here we demonstrate how 3-D Fourier-domain resampling, in combination with high-speed optical coherence tomography (OCT), can achieve high-resolution in vivo tomography. Enhanced depth sensitivity was achieved over a depth-of-field extended in real time by more than an order of magnitude. This work lays the foundation for high-speed volumetric cellular-level tomography.

SDOCT IMAGE RECONSTRUCTION BY INTERFEROMETRIC SYNTHETIC APERTURE MICROSCOPY

Spectral domain optical coherence tomography (SDOCT) is a noninvasive, cross-sectional imaging technique that measures depth resolved reflectance of tissue by Fourier transforming the spectral interferogram with the scanning of the reference avoided. Interferometric synthetic aperture microscopy (ISAM) is an optical microscopy computed-imaging technique for measuring the optical properties of biological tissues, which can overcome the compromise between depth of focus and transverse resolution. This paper describes the principle of SDOCT and ISAM, which multiplexes raw acquisitions to provide quantitatively meaningful data with reliable spatially invariant resolution at all depths. A mathematical model for a coherent microscope with a planar scanning geometry and spectral detection was described. The two-dimensional fast Fourier transform (FFT) of spectral data in the transverse directions was calculated. Then the nonuniform ISAM resampling and filtering was implemented to yield the scattering potential within the scalar model. Inverse FFT was used to obtain the ISAM reconstruction. One scatterer, multiple scatterers, and noisy simulations were implemented by use of ISAM to catch spatially invariant resolution. ISAM images were compared to those obtained using standard optical coherence tomography (OCT) methods. The high quality of the results validates the rationality of the founded model and that diffraction limited resolution can be achieved outside the focal plane.

Interferometric Synthetic Aperture Microscopy: Computed Imaging for Scanned Coherent Microscopy

Three-dimensional image formation in microscopy is greatly enhanced by the use of computed imaging techniques. In particular, Interferometric Synthetic Aperture Microscopy (ISAM) allows the removal of out-of-focus blur in broadband, coherent microscopy. Earlier methods, such as optical coherence tomography (OCT), utilize interferometric ranging, but do not apply computed imaging methods and therefore must scan the focal depth to acquire extended volumetric images. ISAM removes the need to scan the focus by allowing volumetric image reconstruction from data collected at a single focal depth. ISAM signal processing techniques are similar to the Fourier migration methods of seismology and the Fourier reconstruction methods of Synthetic Aperture Radar (SAR). In this article ISAM is described and the close ties between ISAM and SAR are explored. ISAM and a simple strip-map SAR system are placed in a common mathematical framework and compared to OCT and radar respectively. This article is intended to serve as a review of ISAM, and will be especially useful to readers with a background in SAR.

Introduction of Cremaster Muscle Chamber Technique for Long-Term Intravital Microscopy

Objective data comparing sensitivity and accuracy between traditional and computed imaging techniques used for diagnosing mandibular fractures is sparse. To address the paucity of information the authors studied prospectively 33 mandibular fractures in 21 consecutive patients with standard mandibular series, panoramic tomography, axial computed tomography (CT), and coronal CT. Differences in diagnostic accuracy and sensitivity as compiled by four blinded reviewers were calculated. Although overall sensitivities of mandibular fracture detection were not statistically significant between the imaging studies, a distinction between the four methods did exist. Coronal CT was the most accurate imaging method, followed by mandibular series, panoramic topography, and axial CT. Excluding technically inadequate studies, panoramic tomography was 100% accurate and sensitive. Diagnostic accuracy and sensitivity did not correlate measurably with reviewers' impressions of the quality of a particular exam. Axial CT detected significantly fewer angle fractures than standard radiographs (60% vs. 98%, p = 0.006) and coronal CT (60% vs. 100%, p = 0.008). False-positives were unusual except for plain mandibular radiographs. The clear definition of both coronal and axial CT scans made their analysis simpler than the plain radiographs. Lack of fracture displacement was the single most important factor in missed fractures with all modalities. Despite reviewer concerns about the quality of the plain mandibular series, the high accuracy and sensitivity of this imaging technique and applicability in all patients, coupled with its low cost, make it an excellent screening exam for all patients with suspected mandibular fractures. In clinically stable and cooperative patients with mandibular trauma, panoramic radiography and coronal CT are recommended to confirm clinical suspicions when the mandibular series is equivocal. To supplement the mandibular series in the uncooperative or multisystem trauma patient, axial CT scans have not been beneficial. These diagnostic modalities do not obviate the need for a careful physical exam.

Prospective comparison of axial computed tomography and standard and panoramic radiographs in the diagnosis of mandibular fractures.

Objective data comparing sensitivity and accuracy between traditional and computed imaging techniques used for diagnosing mandibular fractures is sparse. To address the paucity of information the authors studied prospectively 33 mandibular fractures in 21 consecutive patients with standard mandibular series, panoramic tomography, axial computed tomography (CT), and coronal CT. Differences in diagnostic accuracy and sensitivity as compiled by four blinded reviewers were calculated. Although overall sensitivities of mandibular fracture detection were not statistically significant between the imaging studies, a distinction between the four methods did exist. Coronal CT was the most accurate imaging method, followed by mandibular series, panoramic topography, and axial CT. Excluding technically inadequate studies, panoramic tomography was 100% accurate and sensitive. Diagnostic accuracy and sensitivity did not correlate measurably with reviewers' impressions of the quality of a particular exam. Axial CT detected significantly fewer angle fractures than standard radiographs (60% vs. 98%, p = 0.006) and coronal CT (60% vs. 100%, p = 0.008). False-positives were unusual except for plain mandibular radiographs. The clear definition of both coronal and axial CT scans made their analysis simpler than the plain radiographs. Lack of fracture displacement was the single most important factor in missed fractures with all modalities. Despite reviewer concerns about the quality of the plain mandibular series, the high accuracy and sensitivity of this imaging technique and applicability in all patients, coupled with its low cost, make it an excellent screening exam for all patients with suspected mandibular fractures. In clinically stable and cooperative patients with mandibular trauma, panoramic radiography and coronal CT are recommended to confirm clinical suspicions when the mandibular series is equivocal. To supplement the mandibular series in the uncooperative or multisystem trauma patient, axial CT scans have not been beneficial. These diagnostic modalities do not obviate the need for a careful physical exam.

Intraoperative imaging of the brain.

The development of computed imaging techniques has revolutionized contemporary neurosurgical procedures. In a 20-year interval, intraoperative imaging was used in more than 4,000 patients at our center. The selection of the appropriate intraoperative imaging tool was dependent on the neurosurgical procedure performed. In our dedicated operating room suite, intraoperative fluoroscopic imaging was used during transsphenoidal, spinal, and functional procedures, e.g. to treat percutaneous trigeminal neuralgia. A dedicated intraoperative computed tomography scanner was first available in 1981 and was used in more than 1,500 stereotactic or image-guided procedures. During radiosurgical procedures with the Gamma Knife (n = 1,560) a variety of intraoperative imaging tools (MRI, CT, angiography, and digital subtraction angiography) were used to define the target. The output of these imaging tools is currently transferred via fiberoptic ethernet to a wide variety of computer workstations designed to facilitate surgical or radiation dose planning. In addition, intraoperative imaging became increasingly important during vascular neurosurgery. Because of its superior patient accessibility and instrument compatibility. CT is likely to remain the most important imaging tool for conventional intraoperative image-guided stereotactic surgery. In contrast, intraoperative MRI proved to be the superior imaging tool for radiosurgery.

On three-dimensional defects in the Ni 3Al( γ′) phase identified by the computed imaging technique

Despite the large number of studies on the plastic properties of L1 2 crystals, the crystalline defects produced by high temperature deformation of phases based on Ni 3Al( γ′) are not yet thoroughly understood. Some examples of unusual three-dimensional defects have been observed in deformed γ′ precipitates of the industrial nickel-based two-phase superalloy CMSX2 and in deformed specimens of the L1 2 alloy 9Al14Ti3.5Cr73.5Ni (atomic percent). These defects, which involve superlattice stacking faults, stair-rod-dislocation-like defects and superpartial dislocations, are analysed by both conventional and high resolution electron microscopy, and the computed imaging technique coupled with two-beam diffraction theory.

Multipath artifact corrections in ultrasonic transmission tomography.

This paper deals with computed imaging techniques for ultrasonic transmission tomography. Cross-sectional images of the refractive index in soft biological tissues can be obtained by measuring the arrival-time of signals that propagate between two transducers. An alternative method to obtain images is to measure the attenuation in the path between the pair of transducers. In practice, images of the refractive index exhibit a better quality than images of the attenuation coefficient. In this report we have shown through computer simulation that some of the degradations in images of the attenuation coefficient are due to the existence of multiple rays that link the transmitting and the receiving transducers. This condition is known as multipath. We have demonstrated two methods to reduce the influence of multipath on reconstructions of the attenuation coefficient. The first method employs homomorphic signal processing to estimate the attenuation coefficient for one of the linking rays. The second method applies median filtering in the projection space to remove the artifacts caused by multipath. The correction techniques were tested on data obtained by scanning tissue equivalent phantoms. Results obtained indicate that the correction methods significantly improve the quality of images of the attenuation coefficient.

Multipath artifact corrections in ultrasonic transmission tomography

This paper deals with computed imaging techniques for ultrasonic transmission tomography. Cross-sectional images of the refractive index in soft biological tissues can be obtained by measuring the arrival-time of signals that propagate between two transducers. An alternative method to obtain images is to measure the attenuation in the path between the pair of transducers. In practice, images of the refractive index exhibit a better quality than images of the attenuation coefficient. In this report we have shown through computer simulation that some of the degradations in images of the attenuation coefficient are due to the existence of multiple rays that link the transmitting and the receiving transducers. This condition is known as multipath. We have demonstrated two methods to reduce the influence of multipath on reconstructions of the attenuation coefficient. The first method employs homonorphic signal processing to estimate the attenuation coefficient for one of the linking rays. The second method applies median filtering in the projection space to remove the artifacts caused by multipath. The correction techniques were tested on data obtained by scanning tissue equivalent phantoms. Results obtained indicate that the correction methods significantly improve the quality of images of the attenuation coefficient.