Dark-field scanning in situ spectroscopy platform for broadband imaging of resected tissue

A dark-field geometry spectral imaging system is presented to raster scan thick tissue samples in situ in 1.5 cm square sections, recovering full spectra from each 100 μm diameter pixel. This spot size provides adequate resolution for wide field scanning, while also facilitating scatter imaging without requiring sophisticated light-tissue transport modeling. The system is demonstrated showing accurate estimation of localized scatter parameters and the potential to recover absorption-based contrast from broadband reflectance data measured from 480 nm up to 750 nm in tissue phantoms. Results obtained from xenograft pancreas tumors show the ability to quantitatively image changes in localized scatter response in this fast-imaging geometry. The polychromatic raster scan design allows the rapid scanning necessary for use in surgical/clinical applications where timely decisions are required about tissue pathology.     

Solution thermodynamics of first row transition elements. 3. Apparent molal volumes of aqueous ZnCl2 and Zn(CIO4)2 from 15 to 55°C and an examination of solute-solute and solute-solvent interactions

The apparent molal volumes of aqueous ZnCl₂ and Zn(ClO₄)₂ solutions have been measured from 15–55°C. The dilute solution data are extrapolated to infinite dilution using the Redlich-Meyer equation. The full concentration range data are fitted with the Pitzer formalism. The data are then compared with the data on the previously measured salts of Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, and Cu²⁺. The effect of complex ion formation is easily seen in the Cu²⁺ and Zn²⁺ salt data. A new approach to single ion volumes from salt volumes is proposed. The calculated ionic volumes at infinite dilution are compared, and it is clear that crystal field effects must be considered in any quantitative theory of transition element volumes.     

Tumor vascular area correlates with photosensitizer uptake: analysis of verteporfin microvascular delivery in the Dunning rat prostate tumor

The parameters that limit supply of photosensitizer to the cancer cells in a solid tumor were systematically analyzed with the use of microvascular transport modeling and histology data from frozen sections. In particular, the vascular permeability transport coefficient and the effective interstitial diffusion coefficient were quantified for Verteporfin-for-Injection delivery of benzoporphyrin derivative (BPD). Orthotopic tumors had higher permeability and diffusion coefficients (Pd = 0.036 microm/s and D = 1.6 microm(2)/s, respectively) as compared to subcutaneously grown tumors (Pd = 0.025 microm/s and D = 0.9 microm2/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large intersubject and intratumor variability exist in the verteporfin concentration, in the range of 25% in plasma concentration and in the range of 20% for tissue concentrations, predominantly due to these microregional variations in transport. However, the average individual uptake of photosensitizer in tumor tissue was only correlated to the total vascular area within the tumor (R2 = 64.1%, P < 0.001). The data are consistent with a view that microregional variation in the vascular permeability and interstitial diffusion rate contribute the spatial heterogeneity observed in verteporfin uptake, but that average supply to the tissue is limited by the total area of perfused blood vessels. This study presents a method to systematically analyze micro-heterogeneity as well as possible methods to increase delivery and homogeneity of photosensitizer within tumor tissue.     

Spectral priors improve near-infrared diffuse tomography more than spatial priors

We compare the benefits of spatial and spectral priors in near-infrared diffuse tomography image reconstruction. Although previous studies that incorporated anatomical spatial priors have shown improvement in algorithm convergence and resolution, our results indicate that functional parameter quantification by this approach can be suboptimal. The incorporation of a priori spectral information significantly improves the accuracy observed in recovered images. Specifically, phantom results show that the maximum total hemoglobin concentration ([Hb(T)]) in a region of heterogeneity reached 91% of the true value compared to 63% using spatial priors. The combination of both priors produced results accurate to 98% of the true [Hb(T)]. When both spatial and spectral priors were applied in a healthy volunteer, glandular tissue showed a higher [Hb(T)], water fraction, and scattering power compared to adipose tissue.     

Alkali Metal- and Ammonium Picrate Extraction and Complex Forming Capabilities of d-Glucose and d-Mannose-based Lariat Ethers

The alkali metal- and ammonium picrate extracting ability of d-glucose- and d-mannose-based 15-crown-5 ethers and related lariat ethers was investigated in dichloromethane – water system. A heteroatom was waried in the crown ether containing a 4,6-O-benzylidene-α-d-glucopyranoside unit 6, (X=O), 2 (X=S) and 8a (X=NH). Extracting ability of the latter species (8a) was excellent (97–99%) in regard of all cations (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺ and NH₄⁺) examined, it was not, howewer, selective. Introduction of a side arm on the nitrogen atom of 8a decreased the extracting ability, but increased the selectivity. In this series of compounds (8b–f, 4), 4 with a pyridylethyl substituent allowed the extraction of sodium picrate in 72%. The glucose-based macrocycles 8a, 8e and 8f formed a stronger complex with the cations examined than the mannose-based analogues 9a, 9e and 9f, that can be explained by the all-gauche conformation of the former ones. It was pointed out that in the case of crowns with tertiary amine moieties, the basicity increases the quantity of the picrates extracted. According to complex forming measurements by FAB-MS, the best sodium ion selectivity was achieved by the γ-hydroxypropyl substituted lariat ether (8e). Possible structures of the complexes formed by the two types of monosacharides with sodium cation were evaluated by molecule modelling calculations.     

Photophysical Properties of Tin Ethyl Etiopurpurin I (SnET2) and Tin Octaethylbenzochlorin (SnOEBC) in Solution and Bound to Albumin

Abstract— The photophysical characteristics of two second-generation PDT photosensitizers, tin ethyl etiopurpurin I (SnET₂) and tin octaethylbenzochlorin (SnOEBC), have been measured in homogeneous solution and when bound to bovine serum albumin (BSA). The ground state and triplet state absorption spectra have been characterized, as have triplet lifetimes and quantum yields for intersys-tem crossing, singlet oxygen formation and photobleaching. In total, these parameters provide a complete set of data that can be used to quantitatively compare the photosensitizing efficiencies of these molecules. The photo-bleaching quantum yield of SnET₂ is increased dramatically when it is bound to BSA, thus limiting the production of singlet oxygen at incident fluences above 1 J/cm². In contrast, the quantum yield of photobleaching of SnOEBC is at least an order of magnitude lower than that of SnET₂ under these conditions and does not significantly limit the photosensitization process for typical in vivo or in vitro fluences. This difference is expected to play a significant role in determining the relative photosensitizing ability of these compounds in vivo.     

Image-guided optical spectroscopy provides molecular-specific information in vivo: MRI-guided spectroscopy of breast cancer hemoglobin, water, and scatterer size

A multimodality instrument that integrated optical or near-infrared spectroscopy into a magnetic resonance imaging (MRI) breast coil was used to perform a pilot study of image-guided spectroscopy on cancerous breast tissue. These results are believed to be the first multiwavelength spectroscopic images of breast cancer using MRI-guided constraints, and they show the cancer tumor to have high hemoglobin and water values, decreased oxygen saturation, and increased subcellular granularity. The use of frequency-domain diffuse tomography methods at many wavelengths provides the spectroscopy required for recovering maps of absorbers and scattering spectra, but the integration with MRI allows these data to be recovered on an image field that preserves high resolution and fuses the two data sets together. Integration of molecular spectroscopy into standard clinical MRI can be achieved with this approach to spectral tomography.     

Rapid magnetic resonance-guided near-infrared mapping to image pulsatile hemoglobin in the breast

A near-IR (NIR) tomography system with spectral-encoded sources was built to quantify the temporal contrast in human breast tissue using guidance from magnetic resonance imaging. The systems were integrated with a custom breast coil interface to provide simultaneous acquisition. The NIR signal was synchronized to simultaneous finger pulse oximeter plethysmogram, which offered a frequency reference. A 0.1 s temporal delay of the absorption pulse within adipose tissue relative to fibroglandular tissue was found, in an initial human study, showing the potential for novel contrast imaging of fast flow signals in deep tissue.