Contrast media for using in medical and diagnostic procedures and methods of using the same

The present invention relates to formulations having low concentrations of contrast agent and/or low Hounsfield values for use in a medical or diagnostic procedure such as imaging or surgery, or for therapeutic use. The present invention also relates to methods for distending or imaging an anatomic segment using the formulations of the present invention. In one alternative embodiment, the formulations of the present invention are especially suitable for use with diagnostic imaging procedures, including, but not limited to, magnetic resonance imaging (MR), computed tomography (CT), ultrasound (US), position emission tomography (PET), and combined modalities such as CT-PET, as well as other medical and therapeutic uses.

Contrast agents are useful in diagnostic imaging because they make it possible to determine the location, size and identity of organs or other structures of the body in the context of their surrounding tissues. In the early days of radiographic contrast development, researchers realized the value of an element\'s density for use as a contrast agent. Barium-based compounds, particularly BaSO4, soon became the preferred contrast agent due to its high atomic weight and its low cost to produce. In addition, its safety profile reinforced this direction of development.

In time, fluoroscopic imaging enabled radiologists to monitor contrast agents as they moved through the GI tract. This advancement required individual BaSO4 suspensions for each segment of the GI tract. Based on the portion of the GI tract being imaged, different contrast media comprising barium sulfate were developed. For the esophagus, a thick paste was used to show esophageal motility and outline the myocardium (heart) and great vessels (aorta) of the thorax. These pastes were high in concentrations of barium sulfate (100% w/v). To study the stomach, a media concentration of barium sulfate (40-80% w/v) was used. In the small bowel, concentrations usually were the same or slightly less as those used for the stomach. Single contrast studies of the colon were performed by rectal administration. Here, sulfate concentrations of 15-18% w/v were used to fill and distend the colon and distal small bowel. In the 1960\'s and 1970\'s, double contrast or air contrast studies were performed on both the upper and lower GI. In these studies, the barium sulfate concentrations for the upper and lower GI were 250% w/v and 100% w/v, respectively.

In the development of computerized axial tomography (“CAT” or “CT”), radiologists used orally administered barium sulfate or dilute iodine solutions to distinguish bowel from other surrounding tissue. Due to the sensitivity of CT, lower concentrations of BaSO4 (2.1% w/v) could be used, as well as dilute iodine solutions.

The introduction of multi-detector helical scanners provided improved quality and image definition. With helical scanner, the current 2.1% barium sulfate concentrations can be used to differentiate the GI tract from the surrounding tissue, but do not allow clear differentiation between bowel wall and bowel lumen. When conventional bowel markets are used the adjacent soft tissues are lost in the image acquisition phase. This is due to a phenomena known as volume averaging. When the radiopaque contrast materials conventionally used are in the bowel lumen, the soft tissue of the bowel wall is lost in the image reconstruction.

The lower contrast media concentrations of the present formulations, when used with, for example, spiral, helical and multi-detector helical scanners (MSMD) in CT and in MR, allows for lumen distention and clear visualization of organs and other structures, for example:

In CT, the newer imaging technology allows for improved image quality and allows image detail of minor HV differences to be appreciated. The conventional oral bowel markers do not allow imagers to take advantage of the bowel marking and imaging of adjacent soft issues. With the older/higher concentration used in conventional CT, the bowel wall is not visualized. The soft tissue next to the dense contrast marking the bowel lumen will cause loss of imaging ability of the adjacent (soft tissue) bowel wall. Much like the penumbra when light passes through space spreading out and including adjacent space reconstruction of high densities in CT casts a shadow on contiguous low density soft tissue structures called “volume averaging.” This concept may be analogized in terms of the CT image being comprised of pixels. Each pixel has a value based on the anatomy it represents if it is bright then it is dense and has a high HV. When you have pixels lined up in a row, as we have in every CT image, there are dense pixels and less dense pixels. When these adjacent pixels have great differences in HV\'s, like we would expect to see in the GI tract bowel wall (45 HV) and the lumen with conventional CT contrast (250 to 450 HV), there is an averaging effect. The pixels of lower density values of the bowel wall are increased and the bowel lumen contrast of higher density pixels are slightly decreased. The net effect is the loss of bowel wall in the image.

There is, therefore, a need for a contrast media having a lower Hounsfield value and/or lower concentration of contrast agent to effectuate high quality imaging of organs or other structures in a medical or diagnostic procedure, or for therapeutic use.

The present invention relates to contrast media formulations having a low concentration of contrast agent and/or low Hounsfield value for use in medical or diagnostic procedures, or for therapeutic use. In one alternative embodiment, the contrast media is comprised of a contrast agent, alone or in combination with a stabilizing agent or osmotic agent. In one embodiment, the present invention is directed to a contrast media having a Hounsfield value less than 250 and preferably less than 100. In another embodiment, the contrast media comprises a contrast agent, such as a barium-based compound. In yet another embodiment, the present invention also relates to formulations and methods for bowel marking, bowel distention and imaging of an anatomic bowel segment of an individual. Additionally, the formulations of the present invention are especially suitable for use with diagnostic imaging procedures including, but not limited to, fluoroscopy (X-Ray), magnetic resonance imaging (MR), computed tomography (CT), CT-PET (position emission tomography and ultrasound (US), as well as other medical and therapeutic uses.