The WCC Note

Your Weekly Guide to Harmonizing Clinical Trial Imaging

Archive for the ‘Nanoparticles’ Category

fMRI: Brain, Imaging Angiogenesis, and Nano-Particles/Cancer – Vol. 2, Number 28

Thursday, December 11th, 2008

fMRI: BRAIN

MRI Helps Translate Thought Into Sound for Man with “Locked-In Syndrome”
When Jean-Dominique Bauby wrote his stunning and transcendent memoir, The Diving Bell and the Butterfly, he communicated it letter by letter by blinking his left eye.  Bauby suffered from “locked-in syndrome,” a rare neurological disorder that paralyzes all voluntary muscles except those controlling eye movements.

For such patients, no means of communication exist except nonvocal ones.  However, a recent article describes an advance which could someday allow these individuals to communicate through sound instead of gestures.  Naturenews reports a study that used an implanted brain electrode to permit a man with locked-in syndrome to create vowel sounds, after using functional brain MRI to assess his speech.

Scientists from Boston University placed the electrode in the speech area of the man’s brain and a computer decoded the brain signals.  The electrode activated a speech synthesizer that accurately replicated three vowel sounds.  As reported at the Society for Neuroscience’s annual meeting in November 2008, the team will subsequently work on computer decoding of consonants to allow the creation of complete words.  Naturenews notes that functional MRI or electrodes placed on the skull could also be used to decode brain speech.

Conclusion:  A man with locked-in syndrome was able to create audible vowel sounds using an implanted brain electrode and speech synthesizer, after having his thoughts analyzed by functional MRI.

IMAGING ANGIOGENESIS

Exploiting Novel Molecules That Create and Comprise Cancer Vessels
The new blood vessels that grow and sustain cancer originate when stimulated to occur by molecules released from cancer cells.  These molecular activators of angiogenesis include a host of proteins and small molecules.  The study of these factors may bring to fruition new and robust imaging for tumor detection and surveillance, as well as innovative therapeutic modalities for tumor cure.  The two molecules thought to be the most important sustainers of tumor growth are vascular endothelial factor (VEGF) and basic fibroblast growth factor (bFGF).  Other activators of angiogenesis include prostaglandins E1 and E2, nicotinamide, and interleukin 8, among others.  The resultant new tumor vessels display their own molecules, providing more investigative avenues to target.  The following article highlights one recent attempt to exploit these molecular features of cancer.

NANO-PARTICLES/CANCER

Imaged Nanoparticles Target Cancer Vessels and Decrease Tumor Size
Integrin ανβ3 comprises one factor found on some tumor vascularity.  Researchers at University of California, San Diego created a nanoparticle targeted at integrin that was linked with the chemotherapeutic agent doxorubicin.  The authors made it fluorescent and injected it into a live mouse pancreatic cancer model.  As reported in Proceedings of the National Academy of Science, the authors noted modest decreased primary tumor growth, but significant reduction in the draining lymph-node metastases.  Featured in Naturenews, the study also reported that the treatment reduced metastases in a mouse kidney cancer model.

Conclusion:  Fluorescent nanoparticles, linked with a chemotherapeutic agent, that were targeted at molecules found exclusively on new vessels have been reported to decrease metastases in mice pancreatic and kidney cancers.

CCTA and MRI: Fibromyalgia & Pancreatic Cancer
Vol. 2, Number 18

Tuesday, July 8th, 2008

MRI: FIBROMYALGIA

Fibromyalgia Patients Demonstrate Different Brain Metabolite Levels on Proton MR Spectroscopy
A study from the University of Michigan investigated brain metabolite differences between people with fibromyalgia (FM) and healthy controls (HC).  The authors sought to test the hypothesis that the broad pain sensitivity experienced by fibromyalgia patients related to a central nervous system processing problem, which would therefore display metabolic alteration in those brain areas involved in processing pain.  Published in the American Journal of Neuroradiology in May 2008, the study examined 21 patients with FM and 27 controls.

Conventional MR was supplemented with 2D-chemical shift imaging (CSI) MR-spectroscopy.  The spectroscopy centered at the basal ganglia and supraventricular white matter.  Within these regions, the study interrogated the spectrographic features of smaller areas implicated in pain processing.  The authors calculated the N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios for each voxel.  They also performed clinical and experimental pain assessments on all the subjects.  The Cho/Cr variability in the right dorsolateral prefrontal cortex proved significantly different in patients with fibromyalgia as compared to controls.  NAA/Cho ratios in the left insula and left basal ganglia showed significant correlations with evoked pain threshold.

Conclusion:  Patients with fibromyalgia demonstrate baseline brain metabolite variability differences compared to health controls.  Those with fibromyalgia also show significant correlation between metabolite ratios and pain parameters.

MRI: PANCREATIC CANCER

Targeted Nanoparticles Image Small Pancreatic Cancers and Cancer Precursor Lesions in Mice
Pancreatic cancer typically eludes detection until the tumor ha reached an incurable state.  In an effort to discover small cancers and precursor lesions that may be curable, researchers at the Massachusetts General Hospital and Dana Farber Cancer Institute developed a novel imaging approach.  The technique exploits the cancer cells’ mutations, which cause different cell-surface proteins to be present than in normal cells.  After detecting several peptides bound to the outside of pancreatic cancer cells but absent on normal cells, an imaging probe was created to make use of this difference.

As reported online in April 2008 by the Public Library of Science, the researchers next found a virus phage clone that bound to these mouse tumor cell peptides.  To accomplish imaging the lesions, the investigators then linked the phages to nanoparticles that had both magnetic and fluorescent properties.  Using mouse models, the nanoparticles allowed detection of small pancreatic ductal carcinomas and precursor lesions.

Conclusion:  The imaging of small and precursor pancreatic adenocarcinomas in mice was accomplished by using nanoparticles linked to viral phages which, in turn, bind to pancreatic carcinoma sell surface peptides.  If the approach can be successfully translated for use in humans, some tumors heretofore typically diagnosed when already incurable could be discovered earlier.

CCTA

Dual-Source Coronary Artery CT Angiography Promising for Atrial Fibrillation Patients
Currently, coronary artery computed tomographic angiography (CCTA) technique relies on imaging the vasculature in the setting of a slow heart rate with regular rhythm.  When tachycardia or irregular beats occur during imaging, image blurring may preclude a diagnostic evaluation of the coronary arteries.  Patients with atrial fibrillation are therefore contraindicated, because faster scanner times than those available with 64-slice, multi-detector scanners would be required.

Authors from Cedars-Sinai Medical Center and University of California-Los Angeles examined dual-source CT (DSCT) for coronary evaluation in 24 patietns with atrial fibrillation (AF) and compared it to 119 control patients in sinus rhythm.  The patients underwent B-blockade to achieve heart rates of 65 beats per minute or less and were also given nitroglycerin.  Bolus tracking was employed with retrospective ECG-gating.  The control group underwent tube current modulation; this was not used in the AF patients to maximize the visualization of all phases of the cardiac cycle.  Patients in both groups had similar coronary calcium scores and prevalence of coronary artery disease.  In the atrial fibrillation group, 2 (8%) of studies proved nondiagnostic, compared to 12 (10%) of the nondiagnostic control group exams.

Conclusion:  Atrial fibrillation patients may be able to undergo diagnostic CCTA in dual-source CT scanners.