Date First Published: March 31, 2017
Date Last Revised: December 20, 2019
This article is still in the process of being written.
Importance of Investigations Data
In addition to information gathered during the process of clinical data gathering, further data collection is accomplished through:
- Monitoring and observations
- Progress review (interview and examination)
In general, further information obtained from investigations is required to:
- Determine or clarify the diagnosis
- Add further details to the patient profile
- Monitor progress of the illness
- Monitor effects of whatever earlier treatment that has been given
Value of Various Types of Investigations
In general, investigations provide data that is objective i.e. more accurate and specific. The information gained can disclose general aspects of the health of the patient or specific changes relating to the disease affecting him/her. Tests that give specific information concerning a disease are used to clarify the diagnosis and are called diagnostic investigations. Usually, diagnosis becomes increasingly more accurate when investigation results clarify the change in morphology (shape, size, depth) and pathophysiology (alteration of function) brought about by the disease.
Tests also help the care-giver to understand the health status of the patient including preexisting health problems and those associated with the disease.
For monitoring progress of the disease and effects of treatment, investigations are repeated so as to detect variations in their values over time. This can be used as the criteria to help indicate:
- disease improvement or deterioration
- effectiveness of the treatment
- occurrence of adverse effects of treatment
Modalities Used for Investigation
Various technology or modalities are used for investigations. They include:
- Imaging studies
- Radio-isotope Scans
- Laboratory tests
- Histopatholgy, Cytology and Cytogenetics
- Endoscopic examination
- Tests of Physiological Function
Salient Features of Various Modalities
Imaging studies make it possible for the clinician to detect changes in morphology (anatomy) of regions and organs caused by disease and in doing so indicate the location and extent of the disease. These changes in appearance include variation in size, shape and extent or the appearance of something unusual (a lesion). The information can point to the organ or tissue involved by the disease, the probable pathology and also show how far the disease has spread. Some examinations may also demonstrate variations in function. Examples include flouroscopy, contrast studies, ultrasound, Doppler ultrasound angiography and radio-isotope studies.
Repeat imaging tests can be used for re-assessment of the progress of the disease by detecting the variation in morphology and function over time.
Plain X-ray (Projection Radiography)
X-rays. a form of electromagnetic radiation, generated by a device called an X-ray tube. X-rays may be absorbed by tissue or when not absorbed penetrate through body parts. Dense tissue like bone absorbs X-rays and to a lesser degree soft tissues (muscles including smooth muscle of walls of intestines and vessels and any organ containing fluid said to be radio dense or radio-opaque. Organs that are less dense or that contains air permit more X-rays to pass through them are said to be radio-lucent.
Radiation that is not absorbed are captured on photographic plates or digital X-ray detector (such as a flat panel detector). These devices will essentially convert the X-rays into black and white images. Normally, parts that capture X-rays are dark or grey while parts where the X-ray have been absorbed will appear white. In order to provide good images, the energy level (voltage applied) of the X-rays are adjusted according to the relative densities of the tissues being imaged and also the depth through which the rays must travel.
The ability of X-ray to differentiate differing consistencies of different tissues allow health care providers to detect changes in shape, size, and position of of various organs and tissues.
In fluoroscopy, the same principles of projection radiography were combined with a fluorescent screen technology or a digital detector screen to view in real time changes due to variation in time due to spontaneous movement of the organ or purposeful manipulation by the care provider.
Fluoroscopy produces X-ray ‘videos’, as it were, allowing for the analysis of tissues or substances as they move within the body, as well as useful supportive imaging for surgeons during procedures. Additionally, these ‘videos’ can now be recorded and stored, of course, whereas in the past they were created in live time but never kept.
Contrast studies is a form of flouroscopy where contrast agents (radio-opaque liquid) are used to outline body cavities or organs with lumen. The test gives information on the following:
- rate of flow of contrast reflecting the propulsive function of the organ
- diameter of the lumen of the organ reflecting on morphologic abnormality
- internal surface characteristics which can give an idea regarding changes in the mucosa
Contrast agents (contrast media) enter the body in one of three ways. They can be:
- swallowed (taken by mouth or orally)
- administered by enema (given rectally)
- injected into a blood vessel (vein or artery; also called given intravenously or intra-arterially)
Following an imaging exam with contrast material, the material is absorbed by the body or eliminated through urine or bowel movements.
There are several types of contrast materials:
- Iodine-based and barium-sulfate compounds are used in x-ray and computed tomography (CT)
- water soluble non-ionic IV contrast media
Contrast materials can have a chemical substance that includes iodine, a naturally occurring chemical element. These contrast materials can be injected into veins or arteries, within the disks or the fluid spaces of the spine, and into other body cavities.
Barium-sulfate is the most common contrast material taken by mouth, or orally. It is also used rectally and is available in several forms, including:
- powder, which is mixed with water before administration
- tablet taken orally to be digested, absorbed and excreted
Oral Contrast Materials
Barium-sulfate contrast materials that are swallowed or administered by mouth (orally) are used to enhance x-ray and CT images of the gastrointestinal (GI) tract, including:
- the small intestine
- the large intestine (colon)
In some situations, iodine-based contrast materials are substituted for barium-sulfate contrast materials for oral administration.
Rectal Contrast Materials
Barium-sulfate contrast materials that are administered by enema (rectally) are used to enhance x-ray and CT images of the lower gastrointestinal (GI) tract (colon and rectum).
In some situations, iodine-based contrast materials are substituted for barium-sulfate contrast materials for rectal administration.
Angiography is a process in which contrast agents are injected into the bloodstream via a guided catheter in order to enable X-ray imaging of our circulation. The resulting angiogram can be either film (capturing movement, like fluoroscopy) or still images. The contrast agent will be a higher density than our blood, enabling high quality images of our blood vessels. Although the term historically implies the use of projected radiography, nowadays CT angiography has emerged as another form of angiography (read more about computed tomography below). Angiography has many applications – among them, detecting a clot (or thrombus) in a vein; evaluating coronary artery disease; locating an aneurysm; or guiding the placement of a stent during a procedure.
Intravenous Contrast Materials
Iodine-based and Gadolinium-based
Iodine-based contrast materials injected into a vein (intravenously) are used to enhance x-ray and CT images. Gadolinium injected into a vein (intravenously) is used to enhance MR images. Typically they are used to enhance or delineate the:
- internal organs, including the heart, lungs, liver, adrenal glands, kidneys, pancreas, gallbladder, spleen, uterus, and bladder
- gastrointestinal tract, including the stomach, small intestine and large intestine
- arteries and veins of the body, including vessels in the brain, neck, chest, abdomen, pelvis and legs
- soft tissues of the body, including the muscles, fat and skin
Biochemical tests are used mainly to determine
- the status of physiological functions
- presence of abnormal cells or tissue
- appearance of an abnormal chemical, cells or material (e.g. markers, abnormal products of metabolism, casts in the urine etc.)
Abnormal results can point to the degree of change in the activity of certain organs or systems. When the results of initial tests performed are taken together with symptoms and signs the data can point to the provisional diagnosis of a certain syndrome. The diagnosis help indicate what further tests need to be done.
Immunology tests are capable of providing specific results. The presence of antigens and antibodies may indicate a certain disease or disease group. Often immunology tests need to be repeated to see a rise in the titre hence demonstrating an active or evolving disease. Immunoassays are useful to detect presence of certain disease causing agents or products of the disease when they are present in very small amounts including microorganisms, antibodies and other proteins produced by the body in response to a disease.
Microbiology tests are used to detect the presence and identification of microorganisms (bacteria, fungi and virus) via direct microscopy, culture and special tests on the organism grown. The tests are done on various body fluids and tissue. Positive results are often diagnostic. Because it is often difficult to detect or grow microorganisms, negative tests may or may not exclude a disease.
Haematology are tests done on blood, bone-marrow or fluids where blood is present. It can indicate changes in the composition, alteration in morphology of cells and presence of abnormal cells. Changes in composition and morphology gives syndromic diagnosis such as anaemia, polycythemia, agranulocytosis, neutropenia and pancytopenia. They make it possible for the clinician to think of various differential diagnosis. Presence of abnormal cells are often diagnostic.
Histopatholgy and Cytology
Histopatholgy, Cytology and Cytogenetics are tests on tissue or cells often taken through biopsy or after surgical removal of an organ or part of it. The tissue or cells are made to react with certain chemicals (stains) or markers and examined under the microscope. Deviation from normal of the tissue structure, the changes in the cells themselves and the extent of spread are looked for. Their findings are often diagnostic.
Endoscopy is the technique of introducing a rigid or flexible tube (the endoscope) to view the internal surface of various hollow organs (the mucosa or endothelium) either directly or using a miniature camera. It provides the means to determine the changes in shape, contour, texture and other morphologic changes. The views can be characteristic of a disease. Via endoscopy, biopsies can be taken for Histopatholgy and Cytology examinations which can then provide a definite diagnosis.
Video or photographs of endoscopic pictures can be kept and used to compare with subsequent examinations for purposes of monitoring and reevaluation.
Tests of Physiological Function
Many tests have been developed to demonstrate the functions of various organs or physiologic systems. These include:
- Pulmonary (lung) function tests
- Tests of cardiac function
- Neuromuscular function tests
- Neurologic tests
- Hearing tests (Audiometry)
- Vision tests (Optometry)
In these tests the patient is attached to a machine and made to perform certain physiologic tasks. Monitoring of signs or activities of the organs involved is performed. Data is collected and interpreted.
For example in a Pulmonary (Lung function test), the patient is asked to breath via mask attached via tubes to the machine which measures volume inspired or expired and the rate of flow of air. Through calculation of these data information can be derived on lung capacity, airway resistance and other parameters of pulmonary function.
Most of these tests are repeatable making them useful for assessment of progress of a function or disease.
Initial investigations are those ordered at the time of initial clinical data gathering or slightly later in order to:
- Clarify the diagnosis
- Add further details to the patient profile
- A particular investigations may be useful for one or both purposes.
Investigations to Clarify the Diagnosis
After the initial clinical data gathering, the diagnosis reached is often of a low-level of accuracy i.e. either a symptom complex or a syndrome. Nevertheless, it provides a pointer to the possible differential diagnosis. The clinician will use the differential diagnosis to decide on the appropriate investigations to perform in order to obtain objective data to narrow down the diagnosis.
Commonly available and relatively simple and inexpensive investigations are usually performed first and may also be done as a routine. Some are available at the clinical work place itself (the point of care). Subsequently, the clinician will order the more specific tests as indicated by the information obtained.
However, if based on history and physical findings the likelihood of a particular diagnosis is high, tests that give fairly specific hence diagnostic results can be ordered. Indeed, where indicated (especially in an emergency), it is not necessary to wait for results of general (routine) tests before performing special complicated tests if such tests would hasten the diagnosis.
Investigations that Add Further Details to the Patient Profile
Besides the changes due to the illness it important to know the health profile of a patient in some detail. Therefore, information from clinical data gathering (by interview and physical examination) is augmented by investigations. Often certain basic investigations are performed routinely for the purpose of detecting:
- certain diseases common among the demographic or social group that the patient belongs to
- certain derangements that the patient already have even before his current illness
- the inconspicuous effects of the current illness on various body systems
This more complete health profile will allow the care provider to anticipate various needs of the patient and provide comprehensive care.
Investigations to Determine the Diagnosis with Certainty
Usually, diagnosis becomes increasingly more accurate as more investigations are done. When the initial investigations point to the possibility of a certain diagnosis, the relevant specific investigations are performed. The clinician can then use the results to determine a diagnosis with a high level of accuracy. Hence, at the beginning, investigations can help the clinician make a diagnosis as syndrome or disease class i.e. together with the symptoms and signs link it to a body system (anatomic and physiologic) or aetiology. Specific investigations make it possible for the clinician to ascertain the diagnosis as a specific disease.
Investigations that Are Diagnostic
Definitive diagnosis is one with a high degree of probability/accuracy because adequate, accurate and pertinent data are available. Usually, the additional more accurate data are derived from or are arrived at from the:
- Results of investigations
- Improved view or access e.g. from endoscopy, examination under anesthesia or surgical exposure
- Subsequent emergence of characteristic patterns of symptoms or signs during observation
- Response to specific treatment
Quite often certain simple investigations can be used to make an accurate diagnosis. This occurs when findings of the tests are peculiar to the disease.
Usually it is the more complex investigations that can be the basis for making a diagnosis with a high level of certainty. Because of the accuracy and specificity of their findings the following investigations are often reliable:
- Imaging studies
- Specific biochemical or immunological tests,
- Demonstration of presence of a particular microorganism via direct microscopy or culture
- Cytological or histopathological examination
Cytological or histopathological findings consistent with the pathology of the suspected disease is deemed the most reliable. However, for most diseases obtaining tissue samples for these tests may not be possible. The test itself may not be applicable for certain diseases. The clinician has to rely on tests that give the clearest possible indication to the type of disease.
Yet at other times, it is the combination of information from various tests, by satisfying a set of criteria, that will satisfy the criteria in making a definite diagnosis.
Positive and Negative Results
A test is useful if it can pick up an abnormality it is supposed to detect. A positive result is when the variation from normal or presence of an abnormal substance is detected. A test result is said to be negative if what is being tested is not found or the result is within normal limits. A result can turn out to be negative if the quantity of substance looked for is too small or if the test is not performed correctly. Sometimes it may be necessary to repeat tests with negative results.
A sensitive test would detect an abnormality easily. If a test is not very sensitive it would fail to provide a positive result in some cases. However, in a very sensitive test, a positive result may not mean that the patient has the disease (false positive). Often, because of this tests are performed in two steps. A fairly sensitive (usually less expensive or complicated) test is used first and a second more specific test is done if the result of the former is positive.
To be diagnostic, a test should only be positive in patients having that particular disease i.e. it is specific to the disease. Some tests may be positive in cases that do not actually have the disease. In that case, it acts as a screening test, a more specific test need to be done or the clinician should consider the result together with data from other tests or other sources.
Usefulness of Tests of Various Modalities for Diagnosis
For example Serum Amylase or Lipase is diagnostic of Acute pancreatitis, direct microscopy of a stained slide of pus may be diagnostic for Gonorrhea.
Immunoassays are used to identify different proteins, hormones and antibodies in blood, urine or other body fluids. The test is based on the reaction of an antigen with an antibody. Antibodies together with suitable markers are usually used as reagents to detect the protein or other molecules (analyte) present in the patient. In some instances, an antigen may also be used as the reagent.
If Monoclonal antibodies i.e. those that are specific to a particualr antigen looked for is used then the presence or abscence of the antigen is usually diagnostic.
Images of bone – for instance, to examine a fracture or for diagnostic measures related to bone conditions like osteoarthritis or certain cancers – require high-energy X-rays because of the high density of bone.
Images of soft tissues like lungs, heart and breasts (both chest X-rays and mammography are very common diagnostic applications of X-rays) require relatively less energy from the X-rays in order to penetrate properly and achieve excellent images.
Spontaneous pneumothorax is diagnosed based on a plain chest x-ray.
Use of Investigation for Monitoring, Reassessment, Progress Review and Re-evaluation
Monitoring is the performance and documentation of planned serial measurements at regular intervals. These information and results are interpreted by comparing them with the condition at the first visit to determine progress. A target measure can also be set to determine whether the treatment objectives are being met. Test of function and levels of certain parameters may be used to anticipate and detect side effects of treatment.
Many of these tests are done regularly and charted on a table or graph. The use of a Laboratory Information System (LIS) is useful for this purpose. Trends can then be discerned. The frequency of measurement of parameters used for monitoring and evaluation selected depends on:
- Nature of the parameter in terms of how rapidly discernible changes occurs
- Desirability (benefit), efficiency and cost effectiveness
Even complex tests such as Microbiological, Hematological tests, Imaging studies and endoscopy may be repeated at planned intervals or when certain events occur. They are useful in evaluating the progress of the disease especially in response to treatment. The findings can help the clinician in deciding to continue, change or cease treatment.
Radiological studies and radioisotope scans (e.g. PET CT) are often repeated to determine progress. Due consideration need to be given to cumulative exposure to radiation. Ultrasound examinations are very suitable for monitoring and evaluation because tehy are relatively easy to do, safe and inexpensive. The ability to store images and retrieve them for comparison is made easy by the use of Radiology Information system (RIS) and PACS system.
Video or photographs of endoscopic captured during sequential examinations can be compared to determine healing or spread.
Images of histologic and cytologic slides before treatment (biopsies) and after treatment (surgical specimen or re-biopsy) can also be compared.