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Integrated imaging – the complementary roles of radiology and nuclear medicine
Imaging techniques are moving towards integrated diagnostic clinical imaging.
Corresponding author: J Warwick (jw@sun.ac.za)
Diagnostic imaging is a dynamic field, which has evolved rapidly
during the past few decades. New modalities have developed and
research techniques have migrated into clinical practice.
Imaging has seen a greater integration of various modalities,
defining the entity of diagnostic clinical imaging sciences.
Nuclear medicine has undergone a metamorphosis over the past 30 years. Established scintigraphic techniques for detecting breaches in the blood-brain barrier and liver masses has been replaced by ultrasound, computerised tomography (CT) and magnetic resonance imaging (MRI). Simultaneously, there has been significant growth in the use of positron emission tomography (PET), sentinel node imaging, targeted radiotherapy and several molecular imaging techniques.
Radiology has experienced exponential growth with regard to helical multi-slice CT scanning using multiple-row detector arrays for the simultaneous collection of data at different slice locations, allowing rapid acquisition of large datasets of longitudinal volumes. The optimal MRI field strength in general clinical practice is 1.5 tesla (T), while 3 T allows mapping of cerebral cortical function by utilising blood oxygen level-dependent (BOLD) imaging. In vivo spectroscopy monitors neuronal viability, cell membrane proliferation and energy metabolism. Current clinical 3 T products have been developed to fit within the physical constraints of 1.5 T platforms by using compact magnets with small fringe fields. Magnets with field strengths of 7 T and even higher are in experimental use.1
An important influence on medical imaging since the beginning of the 21st century has been the increasing availability of hybrid imaging systems. These systems enable a more integrated approach, and define the unitary entity of diagnostic clinical imaging sciences. The concept of hybrid imaging is simple – PET or a single photon emission computed tomography (SPECT) scanner is integrated with a CT scanner on a single platform. The patient is examined using both techniques in immediate succession without any positional changes. Images are fused and displayed by dedicated software. Detailed anatomical imaging combined with the high sensitivity of functional information provides much more information than would be provided by the two individual techniques. The composite images are also generally better appreciated by clinicians.
CT scanners on integrated platforms are mostly high-quality multi-slice diagnostic units. Adding contrast enhancement affords the potential for performing a single comprehensive diagnostic study. PET/MRI, a recent development, is currently being clinically evaluated.
This article highlights clinical scenarios where radiology and nuclear medicine are combined to address specific clinical problems. An exhaustive list of these problems is inapplicable, as unique diagnostic dilemmas continually occur. In our experience, these are best addressed by continuous interaction and regular interdisciplinary meetings.
Oncology
Due to its high sensitivity, PET – using the glucose analogue
[F-18] flourodeoxyglucose (FDG) – is transforming the diagnosis
and management of many malignancies. Integrated PET/CT studies
enhance both accuracy and logistic efficiency. Abnormal FDG
uptake helps the radiologist to scrutinise areas of subtle
anatomical changes, often increasing specificity (Fig. 1). CT
also enhances specificity by localising FDG uptake to
physiological sites, such as brown fat, which on PET alone can
mimic nodal disease. Similarly, the limitations inherent in the
ability of FDG-PET to distinguish a neoplasm from inflammation
are sometimes improved by CT patterns that are more suggestive
of either inflammation or a tumour. PET generally has excellent
sensitivity, while CT detects small lung nodules more
accurately.
Fig. 1. Two cases of the complementary roles of PET and CT, showing an enlarged lymph node identified on CT in a patient with lung cancer negative on PET/CT (A), and Hodgkin’s disease in a patient with involvement of multiple lymph nodes above the diaphragm in which PET identified involvement of a single node in the splenic hilum (B).
Size-based lymph node evaluation for metastatic involvement (short axis >10 mm) and morphology has a low sensitivity and specificity. FDG-PET frequently demonstrates small nodes that are not benign and large nodes that are not metastatic (Fig. 1). FDG uptake has the ability to distinguish residual tumour activity from scar tissue in residual masses after chemotherapy.2
Neuro-endocrine tumours
An integrated approach is essential in
the assessment of neuro-endocrine tumours (NETs). The final
diagnostic analysis combines functional, morphological and
positional information. A detailed radiological work-up is
only possible once a functional lesion has been localised. Localisation
of well-differentiated NETs is performed by using labelled
analogues of somatostatin, or molecules concentrated by NETs.3 Staging
and planning of targeted radiotherapy require functional
techniques, while anatomical imaging is important for monitoring
disease and planning of surgery (Fig. 2).
Fig. 2. Patient with a mass on the greater curve of the stomach on gastroscopy. Histology showed a NET. Whole body somatostatin-receptor imaging with Tc-99m Tekrotyd shows disease restricted to the stomach lesion and a lymph node. These are shown on CT with calcification in the stomach lesion, as well as incidental liver and left kidney cysts.
Musculoskeletal imaging
Bone scintigraphy is a first-line technique for surveying the entire skeleton for metastases in patients with cancer of the breast and prostate, as well as small-cell lung carcinoma. While highly sensitive, the specificity is reduced by numerous benign processes (e.g. degenerative changes, old trauma). Here, radiology has a long-established complementary role, as local radiographs of these sites identify most benign causes of increased activity, whereas normal radiographs are suggestive of metastatic disease.
The sensitivity of MRI depends on focal loss of the T1 signal due to metastatic replacement/destruction of marrow fat cells in trabecular bone. T1 changes appear up to three months before other modalities are positive;4 however, MRI studies are limited by cost and a small field of view, disqualifying it as a viable screening alternative to bone scintigraphy. T1-weighted MRI sequences should be reserved for specific clinical problems, e.g. breast carcinoma with persistent lower back pain, and equivocal focal activity on a bone scan not resolved with plain radiographs. Diffusion-weighted whole-body MRI is an exciting new development with promising results for cancer detection, widely reported in the recent literature.5
Bone scintigraphy plays a complementary
role in benign bone disease, adding sensitivity and enabling
an entire skeletal survey. Most fractures are diagnosed using
conventional radiographs, but bone scanning is a
cost-effective and sensitive means
of detecting fractures, which have a normal appearance on
plain films (e.g. undisplaced, difficult sites) and insufficiency/stress fractures. Scintigraphy
also allows localisation of sites causing back, ankle or foot
pain. When there are subtle or multiple anatomical
abnormalities, active osteoblastic activity can direct
therapeutic interventions to sites requiring relief of pain
(Fig. 3).
Fig. 3. A patient with left foot pain, identified as having accessory navicular bones in both feet on X-ray (A). A bone scan localised the pain source to the accessory navicular bone (B), which is again demonstrated on subsequent a 3D CT reconstruction (C).
Acute osteitis in children can present challenging diagnostic
dilemmas. These children often present as emergency cases,
acutely ill and with raised inflammatory markers. The presenting
complaint may, however, be limited to diffuse bone pain with
normal erythrocyte sedimentation rate (ESR) and white blood cell
(WBC) counts. Plain film examination of the affected limb should
precede special investigations. Ultrasound is an excellent
first-line investigation and is often diagnostic (Fig. 4). CT is
an acceptable alternative, but an MRI study, when available, is
definitive, showing the extent of trabecular oedema and
soft-tissue involvement. Skeletal scintigraphy remains
particularly valuable when MRI availability is limited,
symptoms are poorly localised, or multifocal disease is
suspected.6
Fig. 4. A longitudinal ultrasound section demonstrating a periosteum of a tibial shaft displaced by inflammatory collection in a young patient with clinical signs of infection.
Soft-tissue infection
Ultrasound is normally the first line of investigation, but
MRI, with its superior soft-tissue discrimination, is the
investigation of choice. Inflammatory
processes are identified by a hyperintense signal on T2 STIR
or post-contrast T1 fat saturation sequences. However, an altered
anatomy because of previous trauma or surgery may render
findings equivocal. In these situations the introduction of
infection markers such as labelled WBCs, FDG, and [Ga-67]
citrate assist in the evaluation of disease (Fig. 5). These
tracers are specific and sensitive, demonstrating inflammatory
processes before anatomical changes occur. The choice of
technique depends on the suspected site and chronicity of the
infection. The role of FDG-PET/CT is still being defined, but it
is likely to become important in many of these clinical
scenarios.7
Fig. 5. A patient who required open reduction and internal fixation of a fractured left femur following a gunshot injury. The subsequent development of secondary infection is confirmed on Tc-99m white cell scanning. The presence of a fixation device would affect MRI and CT in this case.
Pulmonary embolism
The imaging of acute pulmonary embolism has advanced with the
widespread implementation of CT pulmonary angiography (CTPA) and
the emerging role of ventilation perfusion (VQ) SPECT (VQS).
CTPA is based on the direct detection of emboli presenting as
filling defects in affected vessels, while VQS images the
functional consequences of the emboli, i.e. underperfused lung
segments (Fig. 6). VQS, using new interpretation criteria,
achieves excellent sensitivity and specificity with few
equivocal studies, and today should be utilised by all nuclear
medicine units.8 Comparative literature
is limited, complicated by the lack of a gold standard, and
confused by comparisons of CTPA with older planar VQ studies.
Fig. 6. Different cases showing pulmonary emboli as a perfusion-ventilation mismatch using VQS (A), and as an arterial filling defect on CTPA (B).
Both CTPA and VQS are excellent first-line investigations and their availability often determines the first choice. Specific considerations such as compromised cardiorespiratory function or structural lung disease favour the use of CTPA when both modalities are available. Similarly, a mosaic perfusion pattern in the appropriate clinical setting on high-resolution CT scans is diagnostic for chronic pulmonary embolism as a cause of unexplained pulmonary hypertension. Conversely, VQS has a significantly lower radiation dose, making its use preferable in pregnancy, in patients with impaired renal function, and in patients in whom prior reactions to contrast media are suspected. Perhaps, most importantly, performing the other examination is useful in those cases where one modality is initially equivocal or discordant with the clinical setting.
Acute cholecystitis
Ultrasound is the initial imaging technique of choice in patients with suspected acute cholecystitis. This is justified in light of its widespread availability and efficacy in the majority of patients. In cases where ultrasound is difficult to interpret (e.g. technically difficult examinations, acalculous disease), hepatobiliary scintigraphy has a high sensitivity and specificity,9 making it an appropriate second-line investigation when clinical suspicion is high.
Liver lesions
Functional imaging with characteristic scintigraphic patterns
can assist with the identification of liver lesions detected on
anatomical imaging (Fig. 7). In liver lesions equivocal for
metastatic disease, increased uptake of FDG on PET/CT
distinguishes metastatic disease from benign lesions. Increased
Tc-99m colloid uptake in a liver lesion is specific for focal
nodular hyperplasia. Haemangiomas show enhancement of
Tc-99m-labelled red blood cells. Developments
in MRI liver contrast media have resulted in substances that
mirror the biodistribution patterns of radionuclide tracers.
Gadolinium chelates are distributed to the interstitial space,
ferumoxides are taken up by Kupffer cells, and the new
mangafodiper agents create T1 shortening after hepatocyte
uptake via the B6 receptor. Exquisite anatomical detail is an
added advantage, but this has significant financial
implications.
Fig. 7. Different cases showing liver
lesions on CT with characterisation being confirmed as
focal nodular hyperplasia with increased Tc-99m colloid
uptake (A), and as haemangioma with intense
Tc-99m-labelled red
blood
cell uptake (B).
Residual splenic tissue
Patients with resistant idiopathic thrombocytopenic
purpura, despite splenectomy, often have continued
destruction of platelets by small amounts of residual splenic
tissue. This tissue is frequently difficult to detect using
anatomical imaging alone. SPECT/CT using Tc-99m-labelled damaged
red blood cells is sensitive and specific for splenic
tissue (Fig. 8), allowing lesions to be located and
guiding their surgical removal.
Fig. 8. Residual splenic tissue identified by Tc-99m white blood cells in a patient with treatment-resistant idiopathic thrombocytopenic purpura, despite a previous splenectomy.
Renal imaging
Ultrasound plays an essential role in many types of renal
disease. The combination of ultrasound and other anatomical
modalities with functional imaging is particularly rewarding
in the renal system. Diuresis renography using Tc-99m MAG-3
clarifies the significance of hydronephrosis and/or
hydro-ureter. Obstructive nephropathy can be ruled out in
patients with a normal diuretic response, while reduced
differential renal function, especially on serial studies,
points to the need for intervention (Fig. 9).
Fig. 9. Bilateral hydronephnosis on CT (A). The renogram shows no obstruction of the left kidney, with normal function and a good response to furosemide at 20 minutes (B). The right kidney has a differential function of only 14% due to obstructive nephropathy.
The distinction between renal artery stenosis and renal vascular hypertension explains the different roles of angiography and captopril renography in the management of these patients. While anatomical imaging is essential for the detection and sometimes for the treatment of stenotic arterial lesions, captopril renography determines the functional significance of lesions, predicts the outcome of interventions, and detects renovascular hypertension related to microvascular disease.
Radiology and nuclear medicine have overlapping roles in the imaging of renal scarring and vesico-ureteric reflux (VUR) in children. A first-time urinary tract infection (UTI) requires ultrasound, which, if normal, obviates the need for further imaging. Children with recurrent UTIs or abnormalities on ultrasound normally require a variety of possible investigations.10 Dimercaptosuccinic acid (DMSA) renal scintigraphy is the most sensitive widely available technique to detect renal scarring. For VUR, a micturating cysto-urethrogram (MCUG) provides important anatomical information, while indirect cystography is a well-tolerated procedure which has a low radiation dose.
Incidental renal masses are being increasingly identified on advanced imaging modalities, more so with present-generation multi-slice CT scanners. A renal pseudotumour due to a prominent column of Bertin shows uptake of Tc-99m DMSA, while renal tumours show no uptake.11
Interventional radiology
The interventional radiologist may be assisted by functional imaging. The choice of an optimal site for taking a biopsy is often facilitated by PET/CT, revealing active disease processes in more accessible sites. Similarly, the use of metabolic information can reduce sampling errors.
Managing gastrointestinal bleeding is challenging when
endoscopy is negative, or difficult to interpret owing to
large amounts of intraluminal blood. Angiography and
embolisation of bleeding sites can be assisted by localisation
of gastrointestinal bleeding sites using Tc-99m-labelled red
blood cells (Fig. 10). Even localisation limited to the major
artery involved prior to angiography can assist with catheter
placement.
Fig.10. Dynamic images on Tc-99m scintigraphy using labelled red blood cells, showing the appearance of activity in the right iliac fossa, localised to the bowel in the ileo-caecal region on SPECT/CT.
The growing utilisation of targeted radiotherapy for palliation of inoperable liver lesions requires close collaboration between the interventional radiologist, who places the catheter in the hepatic artery, and the nuclear medicine physician, who administers the therapy, after scintigraphically confirming correct positioning.
Conclusions
Taking a complementary rather than an
exclusive approach allows for the optimal utilisation of the
diverse spectrum of imaging technologies available. This
philosophy is being practised increasingly with the advent
of hybrid imaging, and the resulting interdependence of
these disciplines. A good understanding of the strengths and
weaknesses of the different modalities available is needed
to achieve this goal. It is the duty of imaging specialists
to develop approaches to clinical problems that are better
integrated, provide improved care, diagnostic accuracy, and
cost-effectiveness. The optimal utilisation of all imaging
modalities, including their complementary strengths,
differing availability, and cost considerations, is arguably
the single most important challenge to all diagnostic
imaging clinicians.
References
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Summary
• A more integrated approach to medical imaging using radiology and nuclear medicine techniques can frequently better address specific clinical problems.
• PET/CT is generally more sensitive and specific for the detection of malignancies than either modality in isolation.
• MRI and bone scan modalities have complementary roles in musculoskeletal imaging.
• Labelled white blood cells, FDG, and [Ga-67] citrate are particularly useful for imaging soft-tissue infections when the anatomical location is altered by previous trauma or surgery.
• CTPA and VQ SPECT are both are excellent first-line investigations for detecting pulmonary embolism.
• Hepatobiliary scintigraphy is a useful second-line investigation for detecting acute cholecystitis if ultrasound is equivocal.
• Characteristic scintigraphic patterns can assist with the characterisation of liver lesions detected on anatomical imaging.
• Renography clarifies the functional significance of hydronephrosis and/or hydro-ureter on anatomical imaging.
• Renal scintigraphy using Tc-99m DMSA can assist in the characterisation of incidental renal masses identified on anatomical imaging.
• PET/CT and labelled red cell studies can assist the radiologist in better directing interventional procedures.
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