Intraductal magnetic resonance imaging of cholangiocarcinoma - a practical possibility.

Intraductal T2 mapping based on a catheter receiver is proposed as a method of visualizing the extent of intraductal and periductal cholangiocarcinoma (CCA). Compared to external receivers, internal receivers provide locally enhanced signal-to-noise ratios by virtue of their lower field-of-view for body noise, allowing smaller voxels and higher resolution. However, inherent radial sensitivity variation and segmentation for patient safety both distort image brightness. We discuss simulated T2 weighted images and T2 maps, and in vitro images obtained using a thin film catheter receiver of a freshly resected liver specimen containing a polypoid intraductal tumor from a patient with CCA. T2 mapping provides a simple method of compensating non-uniform signal reception patterns of catheter receivers, allowing the visualization of tumor extent without contrast enhancement and potentially quantitative tissue characterization. Potential advantages and disadvantages of in vivo intraductal imaging are considered.

Dark field imaging of high aspect ratio structures - a simple model.

A simplified model for dark-field optical imaging of three-dimensional high aspect ratio micro- and nano- structures is proposed, to reduce the time taken to simulate object fields with in-plane scattering between different parts of the object. Primary scattering is found by assuming that illumination of Manhattan geometries generates a set of spherical edge waves, following the incremental theory of diffraction. Secondary scattering is found by assuming that primary scattering is re-scattered from nearby features. Diffraction coefficients are simplified, and the number of illuminating beams is limited to those generating waves that enter the objective lens. Images obtained using TE and TM polarizations are compared, and results are benchmarked against a vectorial finite element model. Applications lie in simulating optical inspection of structures containing vertically etched features including MEMS and NEMS.

Solvent-pumped evaporation concentration on paper in linear and radial geometries.

Solvent-pumped evaporation-driven concentration of an initial distribution of solutes on a porous substrate is considered in one and two dimensions. Approximate analytic solutions to the isotropic advection-dispersion equations are first found for a Gaussian kernel and an infinite domain, following the smoothed particle approximation. Analytic solutions for more general initial distributions are then found as sums of Gaussians, and comparison is made with numerical solutions. In each case, initial distributions are advected toward the stagnation point and concentrated. Two-dimensional analysis is then extended to describe anisotropy in permeability and diffusion, and hydrodynamic dispersion. Radial-flow experiments are performed using filter papers and water-soluble dyes. Diffusion coefficients, temperature and humidity profiles, and the evolution of spot distributions are measured. The results confirm minor anisotropy in permeability and diffusion, limited hydrodynamic dispersion, and largely uniform evaporation. Péclet numbers over 2500 are demonstrated. Evaporation-driven concentration provides a mechanism for solute transport over long timescales. Potential applications lie in the design of paper spray microanalytical devices operating by solvent pumping rather than capillary flow.

Paper-based evaporation concentrators: Comparison of linear and radial geometries.

Paper-based evaporation concentrators with linear and radial geometries are compared. A new method of finding approximate analytic solutions of the advection-dispersion equation is proposed, based on the behavior of concentrators with infinite sources. Analytic approximations are compared with numerical solutions, and the advantage of radial concentration is highlighted: linear concentration rates scale with the square root of the Péclet number Pe while radial rates scale with Pe itself, leading to faster radial concentration beyond a critical value. Experiments are performed with Brilliant Blue FCF dye, using optical transmission and the Beer-Lambert law for quantitation. Dye concentrations are chosen for operation in the linear absorbance regime. Radial concentration is demonstrated under ambient conditions on filter paper disks with 60 mm diameter evaporation areas fed from a perimeter source, in a reverse of the well-known "coffee stain" experiment. Airflow enhanced concentration in strips and wedges is compared directly, using laser-patterned chromatography paper. The advantage of radial concentration is confirmed (and enhanced by diversion of concentrate to the corners of strips) and concentration factors greater than ∼ 500 (the dynamic range of measurement) are obtained in ∼2 h using 30 mm long columns.

In Vitro Intraductal MRI and T2 Mapping of Cholangiocarcinoma Using Catheter Coils.

AIM: Diagnostic imaging of early-stage cholangiocarcinoma is challenging. A previous in vitro study of fixed-tissue liver resection specimens investigated T2 mapping as a method of exploiting the locally increased signal-to-noise ratio (SNR) of duodenoscope coils for improved quantitative magnetic resonance imaging (MRI), despite their non-uniform sensitivity. This work applies similar methods to unfixed liver specimens using catheter-based receivers. METHODS: Ex vivo intraductal MRI and T2 mapping were carried out at 3T on unfixed resection specimens obtained from cholangiocarcinoma patients immediately after surgery using a catheter coil based on a thin-film magneto-inductive waveguide, inserted directly into an intrahepatic duct. RESULTS: Polypoid intraductal cholangiocarcinoma was imaged using fast spin-echo sequences. High-resolution T2 maps were extracted by fitting of data obtained at different echo times to mono-exponential models, and disease-induced changes were correlated with histopathology. An increase in T2 was found compared with fixed specimens and differences in T2 allowed the resolution of tumour tissue and malignant features such as polypoid morphology. CONCLUSION: Despite their limited field of view, useful data can be obtained using catheter coils, and T2 mapping offers an effective method of exploiting their local SNR advantage without the need for image correction.

Improving the Detection of Cholangiocarcinoma: In vitro MRI-Based Study Using Local Coils and T2 Mapping.

AIM: Cholangiocarcinoma is endemic in southeast Asia, generally developing from liver fluke infestation. However, diagnostic imaging of early-stage disease is challenging. The aim of this work is to investigate relaxometry (specifically, T2 mapping) as a method of exploiting the higher signal-to-noise ratio (SNR) of internal coils for improved reception of magnetic resonance signals, despite their non-uniform sensitivity. METHODS: Ex vivo T2 mapping was carried out at 3T on fixed resection specimens from Thai cholangiocarcinoma patients using an mGRASE sequence and an endoscope coil based on a thin-film magneto-inductive waveguide and designed ultimately for internal use. RESULTS: Disease-induced changes including granulomatous inflammation, intraepithelial neoplasia and intraductal tumours were correlated with histopathology, and relaxation data were compared with mono- and bi-exponential models of T2 relaxation. An approximately 10-fold local advantage in SNR compared to a 16-element torso coil was demonstrated using the endoscope coil, and improved tissue differentiation was obtained without contrast agents. CONCLUSION: The performance advantage above follows directly from the inverse relation between the component of the standard deviation of T2 due to thermal noise and the SNR, and offers an effective method of exploiting the SNR advantage of internal coils. No correction is required, avoiding the need for tracking, relaxing constraints on coil and slice orientation and providing rapid visualization.

Mass Spectrometry: A Guide for the Clinician.

Metabolic profiling, metabonomics and metabolomics are terms coined in the late 1990s as they emerged as the newest 'omics' technology at the time. This line of research enquiry uses spectroscopic analytical platforms, which are mainly nuclear magnetic resonance spectroscopy and mass spectrometry (MS), to acquire a snapshot of metabolites, the end products of a complex biological system. Metabolic profiling enables the detection, quantification and characterisation of metabolites in biofluids, cells and tissues. The source of these compounds can be of endogenous, microbial or exogenous origin, such as dietary or xenobiotic. This results in generating extensive, multivariate spectroscopic data that require specific statistical manipulation, typically performed using chemometric and pattern recognition techniques to reduce its dimensions, facilitate its biological interpretation and allow sample classification and biomarker discovery. Consequently, it is possible to study the dynamic metabolic changes in response to disease, intervention or environmental conditions. In this review, we describe the fundamentals of MS so that clinicians can be literate in the field and are able to interrogate the right scientific questions.

Optothermal profile of an ablation catheter with integrated microcoil for MR-thermometry during Nd:YAG laser interstitial thermal therapies of the liver­an in-vitro experimental and theoretical study.

PURPOSE: Flexible microcoils integrated with ablation catheters can improve the temperature accuracy during local MR-thermometry in Nd:YAG laser interstitial thermal therapies. Here, the authors are concerned with obtaining a preliminary confirmation of the clinical utility of the modified catheter. They investigate whether the thin-film substrate and copper tracks of the printed coil inductor affect the symmetry of the thermal profile, and hence of the lesion produced. METHODS: Transmission spectroscopy in the near infrared was performed to test for the attenuation at 1064 nm through the 25 µm thick Kapton substrate of the microcoil. The radial transmission profile of an infrared high-power, light emitting diode with >80% normalized power at 1064 nm was measured through a cross section of the modified applicator to assess the impact of the copper inductor on the optical profile. The measurements were performed in air, as well as with the applicator surrounded by two types of scattering media; crystals of NaCl and a layer of liver-mimicking gel phantom. A numerical model based on Huygens-Fresnel principle and finite element simulations, using a commercially available package (COMSOL Multiphysics), were employed to compare with the optical measurements. The impact of the modified optical profile on the thermal symmetry was assessed by examining the high resolution microcoil derived thermal maps from a Nd:YAG laser ablation performed on a liver-mimicking gel phantom. RESULTS: Less than 30% attenuation through the Kapton film was verified. Shadowing behind the copper tracks was observed in air and the measured radial irradiation correlated well with the diffraction pattern calculated numerically using the Huygens-Fresnel principle. Both optical experiments and simulations, demonstrate that shadowing is mitigated by the scattering properties of a turbid medium. The microcoil derived thermal maps at the end of a Nd:YAG laser ablation performed on a gel phantom in a 3 T scanner confirm that the modified irradiation pattern does not disrupt the thermal symmetry, even though, unlike tissue, the gel is minimally scattering. CONCLUSIONS: The results from this initial assessment indicate that microcoils can be safely integrated with ablation catheters and ensure that the complete necrosis of the liver tumor can still be achieved.

A microelectromechanical systems-enabled, miniature triple quadrupole mass spectrometer.

Miniaturized mass spectrometers are becoming increasingly capable, enabling the development of many novel field and laboratory applications. However, to date, triple quadrupole tandem mass spectrometers, the workhorses of quantitative analysis, have not been significantly reduced in size. Here, the basis of a field-deployable triple quadrupole is described. The key development is a highly miniaturized ion optical assembly in which a sequence of six microengineered components is employed to generate ions at atmospheric pressure, provide a vacuum interface, effect ion guiding, and perform fragmentation and mass analysis. Despite its small dimensions, the collision cell efficiently fragments precursor ions and yields product ion spectra that are very similar to those recorded using conventional instruments. The miniature triple quadrupole has been used to detect thiabendazole, a common pesticide, in apples at a level of 10 ng/g.

Magnetic Resonance Imaging Duodenoscope.

A side-viewing duodenoscope capable of both optical and magnetic resonance imaging (MRI) is described. The instrument is constructed from MR-compatible materials and combines a coherent fiber bundle for optical imaging, an irrigation channel and a side-opening biopsy channel for the passage of catheter tools with a tip saddle coil for radio-frequency signal reception. The receiver coil is magnetically coupled to an internal pickup coil to provide intrinsic safety. Impedance matching is achieved using a mechanically variable mutual inductance, and active decoupling by PIN-diode switching. (1)H MRI of phantoms and ex vivo porcine liver specimens was carried out at 1.5 T. An MRI field-of-view appropriate for use during endoscopic retrograde cholangiopancreatography (ERCP) was obtained, with limited artefacts, and a signal-to-noise ratio advantage over a surface array coil was demonstrated.

Magneto-inductive catheter receiver for magnetic resonance imaging.

A catheter-based RF receiver for internal magnetic resonance imaging is demonstrated. The device consists of a double-sided thin-film circuit, wrapped around a hollow catheter and sealed in place with heat-shrink tubing. Signals are detected using a resonant LC circuit at the catheter tip and transmitted along the catheter using an array of coupled LC circuits arranged as a magneto-inductive waveguide, a form of low frequency metamaterial. Coupling to a conventional RF system is accomplished using a demountable inductive transducer. Protection against external B 1 and E fields is obtained by using figure-of-eight elements with an electrical length shorter than that of an immersed dipole. The system is primarily designed for biliary imaging, can pass the biopsy channel of a side-opening duodenoscope, and is guidewire-compatible, potentially allowing clinicians to implement MR image guided procedures without changing their standard practice. Decoupling against B 1 and E fields is verified, and in vitro (1)H magnetic resonance imaging with submillimeter resolution is demonstrated at 1.5 T using phantoms.

A miniature mass spectrometer for liquid chromatography applications.

A miniature mass spectrometer capable of detecting analytes eluting from a high-performance liquid chromatography (HPLC) system is described and demonstrated for the first time. The entire instrument, including all pumps and the computer, is contained within a single enclosure that may be conveniently accommodated at the base of the HPLC stack. The microspray ion source, vacuum interface, ion guide, and quadrupole ion filter are all microengineered. These components are fabricated in batches using microelectromechanical systems (MEMS) techniques and considered to be consumables. When coupled to a standard HPLC system using an integrated passive split, the limit of detection for reserpine while scanning the full mass range is 5 ng on-column (1 pg of which is passed to the microspray). The mass range is m/z 100-800, and each spectrum is typically acquired at a rate of 1 scan per second.

Optical, thermal, and electrical monitoring of radio-frequency tissue modification.

Radio-frequency (rf) tissue fusion involves the sealing of tissue between two electrodes delivering rf currents. Applications include small bowel fusion following anastomosis. The mechanism of adhesion is poorly understood, but one hypothesis is that rf modification is correlated to thermal damage and dehydration. A multimodal monitoring system capable of acquiring tissue temperature, electrical impedance, and optical transmittance at 1325-nm wavelength during rf delivery by a modified Ligasure fusion tool is presented. Measurements carried out on single layers of ex vivo porcine small bowel tissue heated at approximately 500-kHz frequency are correlated with observation of water evaporation and histological studies on full seals. It is shown that the induced current generates a rapid quasilinear rise of temperature until the boiling point of water, that changes in tissue transmittance occur before impedance control is possible, and that a decrease in transmission occurs at typical denaturation temperatures. Experimental results are compared with a biophysical model for tissue temperature and a rate equation model for thermal damage.

Miniature mass spectrometer systems based on a microengineered quadrupole filter.

Two miniature mass spectrometer systems based on a microengineered quadrupole mass filter have been developed. One of the instruments has a footprint of 27 cm x 20 cm and is intended for laboratory use when space is at a premium. The other is portable and intended for use in the field. It is battery powered, weighs 14.9 kg, and is housed in a rugged case. This is the first example of a portable mass spectrometer incorporating an analyzer fabricated using microelectromechanical systems (MEMS) techniques. The starting material for construction of the filters is a bonded silicon on insulator substrate, which is selectively etched using batch processing techniques to form coupling optics and springs that accurately hold 0.5 mm diameter stainless steel rods in the required geometry. Assembled filters measure 35 mm x 6 mm x 1.5 mm and are mounted, together with an ion source and channeltron detector, in small, interchangeable cartridges, which plug into a 220 cm(3) vacuum chamber. Recovery from accidental contamination or when servicing is required can be achieved within 5-10 min, as the cartridge is easily exchanged with a spare. A potential application to environmental monitoring has been investigated. The headspace above water spiked with dibutyl mercaptan was sampled with a solid phase microextraction (SPME) fiber, which was then injected directly into the vacuum chamber of the mass spectrometer. Using this method, the limit of detection was found to be approximately 5 ppm for a 15 s sampling period.

In vivo 31P magnetic resonance spectroscopy using a needle microcoil.

Batch fabrication methods have been used to produce low-cost microcoils for magnetic resonance spectroscopy (MRS) that could be discarded after applications such as insertion into tissue during interventional surgery. Needle-shaped microcoils were constructed using electroplated conductors buried in shafts formed with different combinations of silicon and plastic and used to acquire in vivo (31)P spectra of rat thigh muscle at 81 MHz. The designs in this study achieved a maximum signal-to-noise ratio (SNR) for phosphocreatine (PCr) of 10.4 in a 10-min acquisition, with the three adenosine triphosphate (ATP) multiplets also clearly visible. An average 20% reduction in PCr occurred over a 60-min period, and intracellular pH was estimated to be 6.6, which are both evidence of ischemia. A needle microcoil design could have applications in real-time MRS of tumors or in evaluating pathology in general during surgical investigations.

Comparison of ion coupling strategies for a microengineered quadrupole mass filter.

The limitations of conventional machining and assembly techniques require that designs for quadrupole mass analyzers with rod diameters less than a millimeter are not merely scale versions of larger instruments. We show how silicon planar processing techniques and microelectromechanical systems (MEMS) design concepts can be used to incorporate complex features into the construction of a miniature quadrupole mass filter chip that could not easily be achieved using other microengineering approaches. Three designs for the entrance and exit to the filter consistent with the chosen materials and techniques have been evaluated. The differences between these seemingly similar structures have a significant effect on the performance. Although one of the designs results in severe attenuation of transmission with increasing mass, the other two can be scanned to m/z = 400 without any corruption of the mass spectrum. At m/z = 219, the variation in the transmission of the three designs was found to be approximately four orders of magnitude. A maximum resolution of M/DeltaM = 87 at 10% peak height has been achieved at m/z = 219 with a filter operated at 6 MHz and constructed using rods measuring (508 +/- 5) microm in diameter.

Real-time optical monitoring of radio-frequency tissue fusion by continuous wave transmission spectroscopy.

Radio-frequency (RF) tissue fusion is a novel method of tissue approximation that can seal tissue without the need for sutures or staples, based on the combined effects of heat and pressure on the apposed tissue surfaces. RF delivery must be controlled and optimized to obtain a reproducible, reliable seal. We use real-time optical measurements to improve understanding of the tissue modifications induced by RF fusion. The main macroscopic transformations are thermal denaturation and dehydration. Light propagation in tissue is a function of both and therefore should provide interesting insight into the dynamic of occurring phenomena. Quantification by continuous wave technique has proven challenging. We proposed an algorithm based on the measurement of the absolute transmittance of the tissue, making use of the modified Beer-Lambert law. The experimental method and the data algorithm are demonstrated by RF fusion of porcine small bowel. The proposed optical measurement modality is well adapted to modern surgical instrumentation used for minimally invasive procedures.