Bulletin of the American Physical Society
APS March Meeting 2011
Volume 56, Number 1
Monday–Friday, March 21–25, 2011; Dallas, Texas
Session D21: Focus Session: Novel Instrumentation & Measurements for Biomedical Research |
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Sponsoring Units: GIMS Chair: Larry Nagahara, National Institutes of Health Room: D161 |
Monday, March 21, 2011 2:30PM - 3:06PM |
D21.00001: Physical principles of genomic regulation through cellular nanoscale structure and implications for initiation of carcinogenesis Invited Speaker: Although compelling evidence suggests that cellular nanoarchitecture and nanoscale environment where molecular interactions take place would be expected to significantly affect macromolecular processes, biological ramifications of cellular nanoscale organization have been largely unexplored. This understanding has been hampered in part by the diffraction limited resolution of optical microscopy. The talk will discuss a novel optical microscopy technique, partial wave spectroscopic (PWS) microscopy, that is capable of quantifying statistical properties of cell structure at the nanoscale. Animal and human studies demonstrated that an alteration in the statistical properties of the nanoscale mass density distribution in the cell nucleus (e.g. nuclear nanoarchitecture) is one of the earliest and ubiquitous events in carcinogenesis and precedes any other known morphological changes at larger length scales (e.g. microarchitecture). The talk will also discuss the physical principles of how the alteration in nuclear nanoarchitecture may modulate genomic processes and, in particular, gene transcription.\\[4pt] Work done in collaboration with Hariharan Subramanian, Prabhakar Pradhan, Dhwanil Damania, Lusik Cherkezyan, Yolanda Stypula, Jun Soo Kim, Igal Szleifer, Northwestern University, Evanston, IL, Hemant K. Roy, Northshore University HealthSystems, Evanston, IL [Preview Abstract] |
Monday, March 21, 2011 3:06PM - 3:18PM |
D21.00002: 3D Cell Culture Imaging with Digital Holographic Microscopy Thomas Dimiduk, Kendra Nyberg, Dariela Almeda, Ekaterina Koshelva, Ryan McGorty, David Kaz, Emily Gardel, Debra Auguste, Vinothan Manoharan Cells in higher organisms naturally exist in a three dimensional (3D) structure, a fact sometimes ignored by in vitro biological research. Confinement to a two dimensional culture imposes significant deviations from the native 3D state. One of the biggest obstacles to wider use of 3D cultures is the difficulty of 3D imaging. The confocal microscope, the dominant 3D imaging instrument, is expensive, bulky, and light-intensive; live cells can be observed for only a short time before they suffer photodamage. We present an alternative 3D imaging techinque, digital holographic microscopy, which can capture 3D information with axial resolution better than $2 \mu m$ in a $100\mu m$ deep volume. Capturing a 3D image requires only a single camera exposure with a sub-millisecond laser pulse, allowing us to image cell cultures using five orders of magnitude less light energy than with confocal. This can be done with hardware costing $\sim\$1000$. We use the instrument to image growth of MCF7 breast cancer cells and p. pastoras yeast. [Preview Abstract] |
Monday, March 21, 2011 3:18PM - 3:30PM |
D21.00003: Carbogen Enhanced Femto Oximetry Breast Cancer Diagnosis Method with High Specificity Bogdan C. Maglich, J.K. Shultis, C.J. Solomon As large malignant tumors are oxygen deficient (hypoxic), cancer could be diagnosed \textit{in vivo} and online, by non-invasive measurement of oxygen difference between tumor and adjacent tissue. Computer simulations of noninvasive diagnosis by Femto Oximetry (FO) of hypoxia in 1 cm tumor in 10 cm breast shows that background $\gamma $'s from non hypoxic tissue will mask hypoxia. To amplify the hypoxic-to-normal O difference, air breathing will be replaced with carbogen (O$_{2}$ 95{\%}, CO$_{2}$ 5{\%}) using vasco-constrictive property whereby carbogen breathing increases O in normal tissue, while not in malignant hypoxic tumors. 90{\%} hypoxia will be detectable by FO with specificity 99{\%}. Our method will be tested on R3230 tumors in Fischer rats at UCI. [Preview Abstract] |
Monday, March 21, 2011 3:30PM - 3:42PM |
D21.00004: Fractal Analysis of Optical Coherence Tomography of Normal and Malignant Breast Tissue Amanda C. Sullivan, John P. Hunt, Amy L. Oldenburg Optical coherence tomography (OCT) provides real-time imaging of tissue several mean free photon paths into tissue by heterodyne detection of backscattered light. OCT can potentially be used to rapidly assess tumor margins during breast cancer resection, however, currently it is difficult to differentiate between normal and malignant tissues with OCT. Because cancer is characterized morphologically by increasing disorder, we investigated the fractal dimension of OCT images of normal and cancerous breast tissue. 3D OCT images of 44 specimens were collected, then tissues were histologically processed to independently determine distinct regions of adipose, stroma and cancer. The fractal dimension of each tissue type was then calculated with a one-dimensional box-counting algorithm applied to the OCT axial scans. We found that the fractal dimensions of stromal tissues were significantly higher than those of cancer (P$<$10$^{-6})$, while those of adipose tissue were significantly lower than those of cancer (P$<$10$^{-4})$. [Preview Abstract] |
Monday, March 21, 2011 3:42PM - 3:54PM |
D21.00005: A new algorithm for detection of apnea in infants in neonatal intensive care units Hoshik Lee, Brooke Vergales, Alix Paget-Brown, Craig Rusin, Randall Moorman, John Kattwinkel, John Delos Apnea is a very common problem for premature infants: apnea of prematurity (AOP) occurs in $>50\%$ of babies whose birth weight is less than 1500 g, and AOP is found in almost all babies who are $< 1000 \, {\rm g}$ at birth. Current respiration detectors often fail to detect apnea, and also give many false alarms. We have created a new algorithm for detection of apnea. Respiration is monitored by continuous measurement of chest impedance (CI). However, the pulsing of the heart also causes fluctuations in CI. We developed a new adaptive filtering system to remove heart activity from CI, thereby giving much more reliable measurements of respiration. The new approach is to rescale the impedance measurement to heartbeat-time, sampling 30 times per interbeat interval. We take the Fourier transform of the rescaled signal, bandstop filter at 1 per beat to remove fluctuations due to heartbeats, and then take the inverse transform. The filtered signal retains all properties except the impedance changes due to cardiac filling and emptying. We convert the variance of CI into an estimated likelihood of apnea. [Preview Abstract] |
Monday, March 21, 2011 3:54PM - 4:06PM |
D21.00006: The Suppression of Dominant Acoustic Frequencies in MRI Xingxian Shou, Robert Brown Patient discomfort and brain imaging distortion are serious MRI acoustic noise problems arising from the rapid switching on and off of gradient coils in the presence of the strong Larmor magnetic field. A study is made of dominant frequencies in the acoustic noise spectrum and, motivated by both spring and string ideas, we propose the cancellation of selected frequencies by appropriate gradient pulse sequence design. From both simulations and experiments, vibrations resulting from an impulsive force associated with a ramping up of a gradient pulse are shown to be cancelled upon the application of another impulsive force coming from the appropriately timed ramping down of that pulse. A method for the suppression of multiple-frequency contributions involving a series of gradient pulses with variable timings is developed and confirmed by experiment. Whether we refer to reduction in terms of dB (about 30-40 dB per peak), or to the verdict of a listener, the conclusion is that a marked reduction in sound can be achieved when at least three of the dominant frequency peaks are suppressed. A variety of pulse profiles and timing combinations can be used to attenuate important contributions to the acoustic spectrum. [Preview Abstract] |
Monday, March 21, 2011 4:06PM - 4:18PM |
D21.00007: Linewidth Narrowing for $^{31}$Phosphorus MRI of Bones Merideth Frey, Sean Barrett Bone is a particularly challenging tissue to study with conventional MRI given the relatively low water density and wider linewidths of its solid components.\footnote{F. W. Wehrli, J. MRI \textbf{25}, 390 (2007); S. Anumula et al., Bone \textbf{42}, 405 (2008); D. Idiyatullin et al., J. Mag Res \textbf{193}, 267 (2008); E.E. Sigmund et al., NMR Biomed \textbf{22}, 436 (2009); Y. Wu et al., J. MRI \textbf{31}, 954 (2010)} Recent fundamental research in quantum computing gave rise to a new NMR pulse sequence that can be used to narrow the broad NMR spectrum of solids.\footnote{Y. Dong et al. Phys. Rev. Lett. \textbf{100}: 247601 (2008); D. Li et al. Phys. Rev. B \textbf{77}: 214306 (2008)} Here we narrow the spectrum of the $^{31}$P in natural bone mineral (by a factor of up to 1600x). This technique offers a new route to do high spatial resolution, 3D $^{31}$P MRI of bone which complements conventional MRI and x-ray based techniques to study bone physiology and structure. Thus far we have used our pulse sequence to do high spatial resolution (sub-250 $\mu$m)$^3$ 3D $^{31}$P MRI of \textit{ex vivo} dry bovine cortical bones, wet procine rib bones, and wet rabbit femoral bones at 4T. We have also explored the use of compressive sampling\footnote{M. Lustig et al., Mag Res Med \textbf{58}, 1182 (2007)} to push imaging time down to less than two hours without distracting artifacts. [Preview Abstract] |
Monday, March 21, 2011 4:18PM - 4:30PM |
D21.00008: Linewidth narrowing for $^{31}$Phosphorus MRI of cell membranes Sean Barrett, Merideth Frey, Joseph Madri, Michael Michaud Most $^{31}$P Magnetic Resonance Spectroscopy studies of tissues try to avoid contamination by a relatively large, but broad, spectral feature attributed to cell membrane phospholipids\footnote{W.J. Thoma et al., J. MR \textbf{61}, 141 (1985); E.J. Murphy et al., MR Med \textbf{12}, 282 (1989); R. McNamara et al., NMR Biomed \textbf{7}, 237 (1994).}. MRI using this broad $^{31}$P membrane spectrum is not even attempted, since the spatial resolution and signal-to-noise would be poor, relative to conventional MRI using the narrow $^{1}$H water spectrum. This long-standing barrier has been overcome by a novel pulse sequence, recently discovered in fundamental quantum computation research\footnote{Y. Dong et al. Phys. Rev. Lett. \textbf{100}, 247601 (2008); D. Li et al. Phys. Rev. B \textbf{77}, 214306 (2008).}, which narrows the broad $^{31}$P spectrum by $\sim$1000$\times$. Applying time-dependent gradients in synch with a repeating pulse block enables a new route to high spatial resolution, 3D $^{31}$P MRI of the soft solid components of cells and tissues. So far, intact and sectioned samples of \textit{ex vivo} fixed mouse organs have been imaged, with (sub-mm)$^{3}$ voxels. Extending the reach of MRI to broad spectra in natural and artificial tissues opens a new window into cells, enabling progress in biomedical research. [Preview Abstract] |
Monday, March 21, 2011 4:30PM - 4:42PM |
D21.00009: Producing $>$60,000-fold room-temperature $^{89}$Y NMR signal enhancement Lloyd Lumata, Ashish Jindal, Matthew Merritt, Craig Malloy, A. Dean Sherry, Zoltan Kovacs $^{89}$Y in chelated form is potentially valuable in medical imaging because its chemical shift is sensitive to local factors in tumors such as pH. However, $^{89}$Y has a low gyromagnetic ratio $\gamma_{n}$ thus its NMR signal is hampered by low thermal polarization. Here we show that we can enhance the room-temperature NMR signal of $^{89}$Y up to 65,000 times the thermal signal, which corresponds to 10 \% nuclear polarization, via fast dissolution dynamic nuclear polarization (DNP). The relatively long spin-lattice relaxation time $T_{1}$ ($\sim$500 s) of $^{89}$Y translates to a long polarization lifetime. The $^{89}$Y NMR enhancement is optimized by varying the glassing matrices and paramagnetic agents as well as doping the samples with a gadolinium relaxation agent. Co-polarization of $^{89}$Y-DOTA with a $^{13}$C sample shows that both nuclear spin species acquire the same spin temperature $T_{s}$, consistent with thermal mixing mechanism of DNP. The high room-temperature NMR signal enhancement places $^{89}$Y, one of the most challenging nuclei to detect by NMR, in the list of viable magnetic resonance imaging (MRI) agents when hyperpolarized under optimized conditions. [Preview Abstract] |
Monday, March 21, 2011 4:42PM - 4:54PM |
D21.00010: Raman spectroscopy as a diagnostic tool to detect head and neck squamous cell carcinoma in archived tissues Suneetha Devpura, Seema Sethi, Jagdish S. Thakur, Vaman M. Naik, Ratna Naik Recently, many spectroscopic techniques are being tried for diagnostic applications. Among them Raman spectroscopy is one of the powerful non-invasive techniques which can differentiate between different biomolecular compositions of tissues on the basis of their vibrational spectra and hence can become an efficient diagnostic tool for detection of cancers. This technique has not yet been explored to study the head and neck squamous cell carcinoma (HNSCC) for archived tissues; here we report its results on HNSCC. Raman spectra were collected from three regions; normal, carcinoma in situ, and carcinoma. The Raman data was analyzed with chemometric methods of principal component analysis (PCA) and discriminant function analysis (DFA). Our preliminary results show that PCA and DFA analysis of Raman spectra can successfully distinguish the pathological states in archived HNSCC tissues. However, large Raman data set from many tissue sections is needed to validate these findings. [Preview Abstract] |
Monday, March 21, 2011 4:54PM - 5:06PM |
D21.00011: Optical measurements of mechanical resonances in biological tissues via magnetic nanoparticle interrogation Vasilica Crecea, Steven Adie, Amy Oldenburg, Renu John, Stephen Boppart We present a real-time phase-resolved optical coherence tomography-based technique that interrogates the mechanical properties of tissue phantoms with different elasticities as well as healthy and cancerous rat tissues, via the interaction of high susceptibility iron oxide nanoparticles that reside inside the samples and an external magnetic field. A chirped magnetic field selects the region of natural resonance in the probed samples as evidenced by scatterer displacements measured with nanometer-level sensitivity. This methodology, entitled magnetomotive optical coherence elastography (MM-OCE), which exploits frequency dependent viscoelastic response in biological media, has potential for detecting tissue pathologies. [Preview Abstract] |
Monday, March 21, 2011 5:06PM - 5:18PM |
D21.00012: Imaging the Vector Magnetic Field of Magnetospirillum Gryphiswaldense by Optically Detected Magnetic Resonance using Nitrogen-Vacancy Centers in Diamond Richelle M. Teeling, Young Woo Jung, Inhee Lee, Justin North, Robin Nakkula, Rohan Adur, Ezekiel Johnston-Halperin, Michael G. Poirier, P. Chris Hammel Nitrogen vacancy centers in diamond are single-spin systems that are stable under ambient conditions with strong optical spin transitions, making them optimal for room-temperature detection of nanoscale magnetic fields using optically detected magnetic resonance (ODMR). We use these ensembles of diamond spins as a scanned probe magnetometer to map the field emitted by Magnetospirillum Gryphiswaldense, in vivo. These bacteria mineralize nanoscale magnetite particles in their internal vesicles. Imaging these living bacteria cells will serve as a strong foundation for the application of our ODMR technique to the medical field, where the bacteria can be used to synthesize functionalized magnetic particles which can be used as biomarkers and targeted drug-delivery systems. [Preview Abstract] |
Monday, March 21, 2011 5:18PM - 5:30PM |
D21.00013: Sub-Nanoparticle Femto Atometry: Measurement of Genome Lengths of Mammalian Tissues Chris Druey, Bogdan C. Maglich, Anna Z. Radovic Measurement of porcine and bovine genome length, giga nucleotide base pairs, Gbp, was made by irradiating each tissue for 30' with neutrons of femto DeBroglie $\lambda \quad \sim $ 10$^{-15}$ m, which, unlike nanoparticles, interact only locally with atomic nuclei in nucleotide. O and C atoms were counted via $\gamma $ rays emitted from (n, n' $\gamma )$ reaction. By irradiating free dA, dC and T nucleotides for 30' we got response constant: (1,450 $\pm $ 44) $\gamma $/O. From 2 measurements we obtained 2.59 $\pm $ .05 and 3.19 $\pm $ .06 Gbp for porcine and bovine, respectively, consistent with 2.7 and 3 Gbp (errors not quoted) obtained by genome sequencing method that took 6 years each. [Preview Abstract] |
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