1/8/11
Magnetic resonance angiography
Time-of-flight MRA showing the circle of Willis in the brain. Note the "venetian blinds" artifact visible as the multiple pseudo-stenosis on both the left and right middle cerebral artery
Magnetic resonance angiography (MRA) is a group of techniques based on Magnetic Resonance Imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of the arteries in order to evaluate them for stenosis (abnormal narrowing), occlusion or aneurysms (vessel wall dilatations, at risk of rupture). MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs (called a "run-off").
Contents
1 Acquisition
1.1 Standard
1.2 Research
2 Artifacts
3 Visualization
4 Clinical use
5 See also
6 External links
Acquisition
A variety of techniques can be used to generate the pictures, based on flow effects or on contrast (inherent or pharmacologically generated).
Standard
Contrast enhanced (CE-MRA): Injection of MRI contrast agents is currently the most common method of acquiring MRA. The contrast medium is injected into a vein, and images are acquired during the first pass of the agent through the arteries. Provided that the timing is correct, this may result in images of very high quality. An alternative is to use a contrast agent that does not, as most agents, leave the vascular system within a few minutes, but remains in the circulation up to an hour (a "'blood-pool agent'"). Since longer time is available for image acquisition, higher resolution imaging is possible. A problem, however, is the fact that both arteries and veins are enhanced at the same time.
Time-of-flight (TOF) or Inflow angiography, uses a short echo time and flow compensation to make flowing blood much brighter than stationary tissue. As flowing blood enters the area being imaged it has seen a limited number of excitation pulses so it is not saturated, this gives it a much higher signal than the saturated stationary tissue. As this method is dependent on flowing blood, areas with slow flow (such as large aneurysms) or flow that is in plane of the image may not be well visualized. This is most commonly used in the head and neck and gives detailed high resolution images.
Phase-contrast (PC-MRA): the phase of the MRI signal is manipulated by special bipolar gradients (varying magnetic fields) that is preset to a maximum expected flow velocity. An image acquisition that is reverse of the bipolar gradient is then acquired and the difference of the two image is calculated. Static tissues such as muscle or bone will subtract out, however moving tissues such as blood will acquire a different phase since it moves constantly through the gradient, thus also giving its speed of the flow. Since phase-contrast can only acquire flow in one direction at a time, 3 separate image acquisitions in all three directions must be computed to give the complete image of flow. Despite the slowness of this method, the strength of the technique is that in addition to imaging the flowing blood, quantitative measurements of blood flow occur at the same time.
Research
Fresh blood imaging (FBI): An imaging technique using fast or super fast spin echo sequences (FSE/SFSE). Takes advantage of the longer T2 relaxation of blood compared to surrounding tissue. The images are acquired by fast spin echo sequences that can be synchronized with heart beats.
4D Dynamic MR Angiography (4D-MRA): The first images, before enhancement, serve as a subtraction mask to extract the vascular tree in the succeeding images. Allows to divide arterial and venous phases of a blood-groove with visualisation of its dynamics. Time of research is much less in comparison with other methods MRA.
BOLD venography or Susceptibility weighted imaging: This method exploits the susceptibility differences between tissues and uses the phase image to detect these differences. The magnitude and phase data are combined (digitally, by an image-processing program) to produce an enhanced contrast magnitude image which is exquisitely sensitive to venous blood, hemorrhage and iron storage. The imaging of venous blood with SWI is a blood-oxygen-level dependent (BOLD) technique which is why it was (and is sometimes still) referred to as BOLD venography. Due to its sensitivity to venous blood SWI is commonly used in traumatic brain injuries (TBI) and for high resolution brain venographies.
Similar procedures to flow effect based MRA can be used to image veins. Called Magnetic resonance venography (MRV) this can be achieved by exciting a plane inferiorly while signal is gathered in the plane immediately superior to the excitation plane, and thus imaging the venous blood which has recently moved from the excited plane. Differences in tissue signals, can also be used for MRA. This method is based on the different signal properties of blood compared to other tissues in the body, independent of MR flow effects. This is most successfully done with balanced pulse sequences such as TrueFISP or bTFE. BOLD can also be used in stroke imaging in order to assess the viability of tissue survival.
Artifacts
MRA techniques in general are sensitive to turbulent flow, which can cause proton spins to rapidly dephased thus causing a significant loss of signal. This can cause mis-diagnosis of stenosis. Other types of MRA related artifacts include:
Phase-contrast:
Phase wrapping: caused by the under estimation of maximum blood velocity in the image. The fast moving blood about maximum set velocity for phase-contrast MRA gets aliased and the flow direction is reversed instead
Maxwell terms: caused by the switching of the gradients field in the main field B0. This cause the over magnetic field to be distort and give inaccurate phase information for the flow.
Time-of-Flight:
Laminar flow: In certain vessels, the blood flow is slower on the vessel walls than near the center. This causes some of the blood near the walls to become saturated further upstream in the vessel.
Venetian blinds: Since the technique acquires images in slabs, non-uniform flip angles due to uneven distribution of the sinc pulses resulting in non-uniform signal intensity
Visualization
Maximum intensity projection of an MRA covering from the top of the heart to just below the circle of Willis
Occasionally, MRA directly produces (thick) slices that contain the entire vessel of interest. More commonly, however, the acquisition results in a stack of slices representing a 3D volume in the body. To display this 3D dataset on a 2D device such as a computer monitor, some rendering method has to be used. The most common method is Maximum intensity projection (MIP), where the computer simulates rays through the volume and selects the highest value for display on the screen. The resulting images resemble conventional catheter angiography images. If several such projections are combined into a cine loop or QuickTime VR object, the depth impression is improved, and the observer can get a good perception of 3D structure. An alternative to MIP is direct volume rendering where the MR signal is translated to properties like brightness, opacity and color and then used in an optical model.
Clinical use
MRA has been successful in studying many arteries in the body, including cerebral and other vessels in the head and neck, the aorta and its major branches in the thorax and abdomen, the renal arteries, and the arteries in the lower limbs. For the coronary arteries, however, MRA has been less successful than CT angiography or invasive catheter angiography. Most often, the underlying disease is atherosclerosis, but medical conditions like aneurysms or abnormal vascular anatomy can also be diagnosed.
An advantage of MRA compared to invasive catheter angiography is the non-invasive character of the examination (no catheters have to be introduced in the body). Another advantage, compared to CT angiography and catheter angiography, is that the patient is not exposed to any ionizing radiation. Also, contrast media used for MRI tend to be less toxic than those used for CT angiography and catheter angiography, with less people having any risk of allergy. Also far less is needed to be injected into the patient. The greatest drawbacks of the method are its comparatively high cost and its somewhat limited spatial resolution. The length of time the scans take can also be an issue, with CT being far quicker. It is also ruled out in patients who are unsafe for MRI (such as having a pacemaker or metal in the eyes or certain surgical clips).
1/5/11
Updated USP standards for PET drugs used in nuclear medicine, radiology ... - pharmabiz.com
New quality assurance standards for the production and compounding of Positron Emission Tomography (PET) drugs are being proposed by the US Pharmacopeial Convention (USP)-the scientific, non-profit organization responsible for establishing quality standards for pharmaceutical products marketed in the United States. USP is seeking public comment on revisions to General Chapter <823>, Radiopharmaceuticals for Positron Emission Tomography-compounding, until March 31, 2011.
Used to aid in diagnosing disease and assessing specific health concerns, PET drugs are radioactive drugs administered to patients so that a specialized scanner can take images of internal organs and tissues. Unlike X-ray or MRI images, which show only body structure, PET images show the chemical functioning of organs or tissues. PET drugs contain a small amount of radioactive material and must be administered to patients within a few hours of being produced, making it necessary for drug production to occur as needed in a manner that ensures their identity, strength, quality and purity.
Most individual PET drug monographs and chapters in USP-NF were published in the 1990s. Although PET drugs primarily were developed as research and investigative tools, the environment in which they have been produced and used over the last decade has changed significantly. This includes: expanded use and supply of PET drugs in routine diagnostic imaging; the potential use of PET imaging agents as tools to accelerate and reduce the cost of traditional drug discovery efforts; and the development of new routine diagnostic imaging agents for use in cardiology, oncology and neurology. Diversification of PET production and use prompted USP to review trends and changes in this area, which led to the conclusion that the current version of Chapter <823> does not fully meet the needs of today's PET drug environment.
Among the areas addressed by the proposed revisions to General Chapter <823> are: differences between the organization of <823> and the provisions of the Food and Drug Administration (FDA) Final Rule and Guidance issued for PET drugs in 2009 Defined frequency for certain quality control tests, timing of completion of certain QC tests relative to product release, given the short time frame in which a PET drug must be administered after its production Inclusion of requirements for out-of-specification (OOS) investigations for QC tests.
Whatever version of <823> is current is always applicable, with compendial requirements enforceable by FDA under the adulteration provisions of the Federal Food, Drug, and Cosmetic Act (FDCA 501(b)). However, USP's PET standards also have a special role under FDA's Current Good Manufacturing (CGMP) requirements. When the FDA Modernization Act became law in 1997, it required that PET drugs be compounded according to USP monographs and general chapters until FDA established CGMP regulations for PET.
In 2005, FDA issued a proposed rule for PET CGMP and indicated that different CGMP requirements should be applied to investigational and research PET drugs to allow more flexibility during the development of these drugs. FDA determined that <823> would be adequate to ensure that investigational and research PET drugs are produced safely. In 2009, FDA issued final regulations and an accompanying guidance document for PET CGMP. The new CGMP requirements are codified in the Code of Federal Regulations Title 21 Part 212 (Part 212) and are aimed at PET drugs with marketing-approval status or potential (as opposed to those for investigational or research use).
When Part 212 becomes effective on December 12, 2011, the CGMP requirements for investigational and research PET drugs may be met by complying with either Part 212 or USP's General Chapter <823> (1998 version). All other PET drugs (not for investigational or research uses) are expected to meet CGMP stipulations of Part 212. Based on the feedback received during the public comment period, USP will determine whether additional review of the <823> revisions will be necessary or if the chapter is then suitable for publication. Once the revised <823> is published, USP will petition FDA to update its reference to cite the newly revised version in its regulation. Until that is accomplished, investigational and research PET drug manufacturers will have to comply with the 1998 version of <823> or the Code of Federal Regulations Title 21 Part 212 to meet CGMP requirements.
The United States Pharmacopeial Convention (USP) is a scientific, non-profit, standards-setting organization that advances public health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods. USP's standards are relied upon and used worldwide.

