When we think of Magnetic resonance we think of the massive multimillion dollar magnetic resonance imaging machines into whose gaping mouth we are slowly propelled on a motorized table, ready to have our smallest flaws exposed. But the phenomenon of magnetic resonance has other medical uses. A team of physicians and scientists led by Prof. Ralph Weissleder of Massachusetts General Hospital (MGH) has developed a handheld diagnostic magnetic resonance (DMR) device that can diagnose cancer in an hour with greatly improved accuracy compared to the current gold standard. The DMR technique is sensitive enough that only material from a fine needle aspiration biopsy is needed for the test - a far less painful experience compared to the usual surgical or core needle biopsies.

## Magnetic Resonance

The principle underlying magnetic resonance can be illustrated by imagining a magnetic compass, which is a small magnet free to pivot around a balance point. The magnetic force between the magnet and the Earth's magnetic field causes the compass to align along the Earth's magnetic field – the needle points north. But as the needle settles down, it oscillates clockwise and counterclockwise from the ideal alignment with the Earth's field. This oscillation has a characteristic rate called the magnetic resonance frequency.

Now comes the tricky part. Place the compass between the poles of an electromagnet so that the field of the electromagnet is perpendicular to that of the Earth, and replace the Earth's magnetic field by a static magnetic field from a magnet. If you send a DC current through the electromagnet, the compass needle just shifts into a new alignment. However, if you power the electromagnet with AC current, the compass needle will oscillate back and forth.

If the frequency of the AC current is equal to the magnetic resonance frequency, there will be a net transfer of energy to the compass needle – it will vibrate more and more strongly as the needle absorbs energy from the AC magnetic field. When the needle gains energy from the AC field, it is necessary to provide more energy to the AC field to compensate for those losses. DMR detects magnetic spins in a sample by measuring the power lost from the AC magnet.

## The DMR device

Weissleder's DMR is the worldʼs smallest cancer diagnostic system, and one of the smaller magnetic resonance devices as well. The huge superconducting magnet is replaced by a permanent magnet 8 cm (3.15 inches) in diameter and 5.5 cm (2.17 inches) in height. The magnet is designed for small scale DMR applications, providing a 1.2 cm (0.5 inch) region of constant magnetic field between the poles of the magnet. The strength of the magnetic field is 0.5 Tesla, rather small compared to the 1.5 to 3 Tesla fields of most MRI machines, but still 10,000 times the strength of the Earth's magnetic field.

The DMR probe, which is placed in the constant field region of the permanent magnet, consists of a microfluidic network in which the biopsy specimens are mixed with the antibody-tagged magnetic particles, a DMR sample chamber, and the microcoils that apply an AC magnetic field to the sample. The DMR electronics are made of commercial integrated circuits, including a microcontroller, a radio frequency (RF) generator, a data acquisition unit, and an RF transceiver, all fitting into a modular platform about 20 cm x 8 cm (8 x 3.15 in) across. The estimated cost of the instrument is a few thousand U.S. dollars.

## Cancer diagnosis

The MGH team performed a series of biotagging experiments, in which nano-sized magnetic particles were attached to antibodies targeted for specific cellular markers of cancer. When these tagged magnetic particles were mixed with cellular material from a patient biopsy, their antibodies attach onto sites on the cell membranes expressing that cancer marker. The magnetic resonance signal from the magnetic markers then indicates the presence of a particular cancer marker in the biopsy sample.

Weissleder's team quickly discovered that none of the cancer markers tested act as a "smoking gun." It requires a diagnostic panel of several cancer markers to obtain a clear diagnosis of cancer. His team tested biopsied tumor material from 50 cancer patients, looking for the presence or absence of any of a set of 12 cancer markers. By searching for patterns within their experimental results, they discovered a set of four cancer markers whose DMR signals, properly weighted, indicated the presence of cancerous cells in 48 of the 50 patients.

This diagnostic panel was then applied to an additional set of 20 patients, and the presence of cancer was confirmed in all 20 patients. The conventional gold standard test, which uses chemical stains and visual inspection under a microscope, is roughly 84 percent accurate, compared to the better than 96 percent accuracy of the DMR test. The conventional test generally has a turn-around time of two to three weeks before receiving the results, compared to an hour for the DMR test.

The basic approach of the MGH DMR test can be applied to diagnosis of a large number of diseases that usually require long turnaround times and/or large tissue samples. Let's hope that, should you or a loved one face the big C, you find a DMR in your oncologist's office!